Handbook of Oxidative Stress in Cancer: Therapeutic Aspects

Description

This reference book, which is the second volume of Targeting Oxidative Stress in Cancer, explores oxidative stress as the potential therapeutic target for cancer therapy. The initial chapters discuss the molecular mechanisms of oxidative stress and its effects on different signaling pathways. Subsequently, the sections examine the impact of redox signaling on tumor cell proliferation and consider the therapeutic potential of dietary phytochemicals and nutraceuticals in reactive oxygen species (ROS)-induced cancer. In turn, it examines the evidence supporting the use of Vitamin C in cancer management, before presenting various synthetic and natural compounds that have therapeutic implications for oxidative stress-induced cancer. It also explores the correlation between non-coding RNA and oxidative stress. Furthermore, the book summarizes the role of stem cells in ROS-induced cancer therapy and reviews the therapeutic applications of nanoparticles to alter redox haemostasis in cancer cells. Lastly, it explores heat-shock proteins, ubiquitin ligases, and probiotics as potential therapeutic agents in ROS-mediated cancer. This book is a useful resource for basic and translational scientists as well as clinicians interested in the field of oxidative stress and cancer therapy. ​ Preface Contents About the Editor Contributors Part I: Therapeutic Implications of Natural Compounds 1 Elimination of Senescent Cells by Polyphenols and Flavonoids Introduction Cellular Senescence Markers of Cellular Senescence Senescence-Associated Mitochondrial Dysfunction (SAMD) Senescence-Associated Secretory Phenotype (SASP) Bystander Effect Therapy-Induced Senescence (TIS) TIS Induced by Polyphenols Escape From TIS Senescent Cells: A Survival Niche Generating a Complex Tumor Environment Importance of TIS by the Example of Radiotherapy-Induced Senescence Role of TIS in Other Cancer Treatments Polyphenols Inhibiting SASP (Senostatics) Apigenin Epigallocatechin-3-Gallate (EGCG) Resveratrol Quercetin Polyphenols as Senolytics (Polyphenols Killing Senescent Cells) Fisetin Quercetin Epigallocatechin-3-Gallate (EGCG) Curcumin Herbal Extracts with Senolytic and Senomorphic Properties Extract of the Plant Solidago virgaurea Subsp. alpestris Alcoholic Extract of Ajuga taiwanensis Pinellia ternata Tuber Olive Plant Conclusion References 2 Natural Dietary Alkaloids and Its Synthetic Derivatives as Oxidative Stress-Inducing Agents for Cancer Therapy Introduction Berberine Piperine Neferine Piperlongumine Conclusion References 3 Natural Therapeutic Strategies for Modulating Oxidative Stress in Cancer Introduction Oxidative Stress and Carcinogenesis Antioxidant Defense Mechanism Oxidative Stress and Natural Compounds The Role of Antioxidant Potential of Phytochemicals in Oxidative Stress Mechanism of Natural Compounds in Combination with Chemotherapy Marine Product with Antioxidative Stress Activity Microbial Antioxidative Stress Compounds Conclusion Future Perspective References 4 Antioxidant in Cancer Introduction Reactive Oxygen Species (ROS) Reactive Oxygen Species (ROS) in Cancer Antioxidants Antioxidants Types Defense Mechanism of Antioxidant Antioxidant: Preventer of Cancer Antioxidant: Promoter of Cancer Antioxidant: An Achilles´ Heel The Antioxidant Conundrum: Friend or Foe Conclusion References 5 Antioxidant Activity of Phytochemicals in Cancer Introduction Role of Reactive Oxygen Species (ROS) in Cancer Progression ROS and Chemoresistance Development Cellular Redox System and Molecular Mechanisms Against ROS Phytochemicals and Their Antioxidant Activity in Cancer Triphala Resveratrol Indole-3 Carbinol (I3C) Peucedanum Chenur Astaxanthin Quercetin Ellagic Acid Caryophyllene Sesquiterpenes Phlorotannins The Antioxidant/Pro-oxidant Enigma of Cancer Therapy Phytochemicals as Immunotherapy Adjuvants Conclusion and Future Perspectives References 6 Therapeutic Application of Microbial Metabolites in Free Radical-Induced Tumorigenesis Introduction Role of ROS in Tumorigenesis Antioxidant Compounds from Microbial Sources Role of Secondary Metabolites of Actinobacteria in Anticancer Activity Role of Exopolysaccharides of Lactic Acid Bacteria in Anticancer Activity Effect of Bacterial Toxins and Enzymes on Anti-tumorigenesis Role of Biosurfactants from Microorganisms in Antitumor Therapy Conclusion and Future Perspectives References 7 Therapeutic Potential of Natural Agents Against Oxidative Stress-Influenced Colitis-Associated Cancer Introduction Colitis-Associated Cancer (CAC) Sources of Free Radicals in the Colon Food Obesity Age Reactive Oxygen Species (ROS) Role of ROS in CAC Natural Agents and Its Mechanism of Action on CAC Mechanism of Action of Procyanidin B on CAC Mechanism of Action of Shaoyao Decoction on CAC Mechanism of Action of Red Ginseng Oil on CAC Mechanism of Action of Caffeic Acid Phenethyl Ester on CAC Mechanism of Action of Lyophilized Acai Pulp on CAC Protocatechuic Acid on CAC Betaine on CAC Sasa quelpaertensis Leaf Extract on CAC Oligonol on CAC Embelin on CAC Phytosomal Curcumin on CAC Rutaecarpine on CAC Vanillin on CAC Huangqin Decoction on CAC American Ginseng on CAC Hydroxychloroquine on CAC Conclusion Future Directions References 8 Oxidative Stress: A Double Edged Sword in Cancer Introduction Tetrandrine as ROS Scavenger Tetrandrine-Induced ROS-Mediated Autophagy Tetrandrine-Induced ROS-Mediated Apoptosis Conclusion References 9 Prevention of Fertility due to Chemotherapy-Induced Ovarian Failure: Role of Therapeutic Antioxidants Introduction Types of Cytotoxic Drugs Pathways of Chemotherapy-Induced Ovarian Damage Chemotherapy-Induced Oxidative Stress Cellular Background of Oxidative Stress Redox State and Oxidative Stress Antioxidant System and Use of Antioxidants During Chemotherapy Adjuvant Antioxidants Vitamin C and Vitamin E Melatonin Other Antioxidants Conclusion and Future Perspective References 10 Therapeutic Implications of Phytochemicals in ROS-Induced Cancer Introduction Reactive Oxygen Species in Cancer Carcinogenesis and Phytochemicals Chemoprevention: Types and Approaches Dietary Phytochemicals: Role in Cancer Chemoprevention Phytochemicals: Polyphenols Flavonoids Apigenin Isoflavonoids Anthocyanidins Phytoestrogens Resveratrol Curcumin Terpenoids Carotenoids Lycopene Limonoids Glucosinolates α-Linolenic Acid (ALA) Allicin Silymarin Sulforaphane (SFN) Conclusions References 11 Nutraceuticals in Cancer Therapy Introduction Nutraceuticals and Cancer Flavonoids and Polyphenols Catechins Theaflavins and Thearubigins Flavonoids Non-flavonoidal Anti-cancer Nutraceuticals Organosulfur Compounds Sulforaphane (SLFN) Glucobrassicin and Indole-3-Carbinol Diallyl-Disulfide and Thiosulfinates Carotenoids Resveratrol Curcumin Cancer and Diet Molecular Biology Effects Effect of Nutritional Support on Cancer Patients Nutraceuticals: Challenges and Perspectives Conclusion References 12 Potential Natural Product-Derived Compounds for Lung Cancer Therapy Lung Cancer Types and Staging of Lung Cancer Lung Cancer and Oxidative Stress Potential Sources Oxidative Stress and Biological Effects Apoptotic Cell Death and Oxidative Stress Apoptosis Potentials Targets of Drug Action in Relevance to Reactive Oxygen Species and Redox Regulation Misfolded Proteins, Reactive Oxygen Species (ROS), and the Endoplasmic Reticulum Stress (ER Stress) ER Stress as a Target for Lung Cancer Treatment CSC and Oxidative Stress in Lung Cancer Natural Product Derived Compounds New Anticancer Compounds from Plants Gallic Acid Curcumin Flavonoids Green Tea Polyphenols Genistein Tangeretin Resveratrol Lectins Natural Product-Derived Compound Regulating Mitochondrial Pathway Gracillin Quercetin Resveratrol Pterostilbene Honokiol Betulinic Acid Marine-Derived Compounds for Cancer Treatment Ecteinascidin Alkaloids Psammaplin A Didemnin B Dolastatin 10 Halichondrin B References 13 Role of Dietary Antioxidants in Chemoprevention of Nitrosamines-Induced Carcinogenesis Introduction Causes of Chemical Carcinogenesis Carcinogenicity of N-nitroso Compounds Dietary Cancer Prevention Chemoprevention Dietary Intervention Lycopene Vitamins Carotenoids Isothiocyanates Polyphenols Flavonoids Calcium Astaxanthin Conclusion Future Direction References 14 Natural Antioxidants for the Prevention and Treatment of Cancer Introduction Free Radicals, Oxidative Processes, and Cell Changes Secondary Metabolites, Sources, and Nutritional Implications Herbal Bioactive Compounds and their Molecular Targets Benefits and Risks of Concomitant Use of Secondary Metabolites and Cytotoxic Drugs Novel Uses of Secondary Metabolites in Cancer Research Conclusions and Future Directions References 15 Protective Effect of Quercetin, Luteolin, and Fisetin via Stimulating the p53-Mediated Signaling in Cancer Introduction Structure of p53 Regulation of p53 Level and Activity Physiological Functions of p53 Cell Cycle Regulation Induction of Apoptosis p53 in Response to DNA Damage p53 Targets Survival Signaling p53 and Its Cross Talk with Other Signaling Pathways p53 and Its Cross Talk with NF-κB p53 and Oxidative Stress Conclusion Future Perspective References 16 Flavonoids and Its Anticancer Activity for ROS-Induced Breast Cancer Introduction ROS Level and Cellular Homeostasis ROS in Cancer Signaling Pathway Flavonoids as Anticancer Agents Chemistry and Classification Absorption, Metabolism, and Bioavailability of Flavonoids Anticancer Effects of Flavonoid Effect of Flavonoids on Breast Cancer Molecular Mechanism of Action Flavonoids for Breast Cancer Conclusion References 17 Role of Indian Ginseng Withaferin A in ROS-Induced Cancer Chemoprevention and Cancer Therapy Introduction Plant Distribution and Phylogeny Chemical Constituents of Ashwagandha Roots Pharmacological Effects of Withania somnifera Anti-inflammatory Properties Antioxidant Activity Adaptogenic Property Antiangiogenic Property Immunomodulatory Activity Other Activities of Withania somnifera Reactive Oxygen Species (ROS): Double-Edged Sword Reactive Oxygen Species (ROS) Antioxidant System Signaling Pathways Mediated by ROS PI3/Akt Pathway Mediated by ROS MAPK Pathway Mediated by ROS Keap1-Nrf2-ARE Pathway Mediated by ROS NF-B Pathway Mediated by ROS ROS, a Driving Force for Tumorigenesis ROS-Mediated Chemoprevention Withaferin A in ROS-Induced Chemoprevention Conclusion References 18 Role of Carotenoids in Preventing Oxidative Stress–Induced Cancer Introduction Oxidative Stress Antioxidants Carotenoids Sources of Carotenoids Carotenoid Biosynthesis Structural Features of Carotenoids General Functions of Carotenoids β-Carotene Lycopene Lutein Zeaxanthin β-Cryptoxanthin Astaxanthin Canthaxanthin Fucoxanthin Future Perspectives of Carotenoids References 19 Role of Honey in Prevention and Management of Cancer Introduction Bioactive Components of Honey Sugars Polyphenols Amino Acids Proteins and Enzymes Vitamins and Minerals Mechanistic Perspective of Honey in Combating Cancer Honey Induces Apoptotic Cell Death Honey Regulates the Mitochondrial Pathways and Related Proteins Honey Induces ROS, and This Arrests Cell Cycle Anti-inflammatory and Immune-Modulatory Effects of Honey Role of Honey in Combating Metastasis and Stem Cell Populations Honey as a Combinatorial Approach for the Management of Cancer Cautions for the Use of Honey Conclusions References 20 Natural Extracts Target NF-κB and Reactive Oxygen Species Introduction Reactive Oxygen Species (ROS) and Their Role in Cancer Promotion of Tumor Cell Proliferation by ROS ROS-Mediated Regulation of Apoptosis and Cell Survival Role of ROS in Cell Motility and Metastasis Role of ROS in Angiogenesis ROS in Cancer Stem Cells (CSCs) and Promotion of Chemoresistance ROS-Mediated Antitumorigenic Activity NF-kappa B (NF-κB) Signaling and Tumor Progression NF-κB Signaling NF-κB and Oncogenesis Chemoresistance Mediated by NF-κB and ROS Folate Antagonists or Antifolates Pyrimidine Antagonists Alkylating Agents Intercalating Agent Mitotic Spindle Inhibitors Use of Natural Extracts to Prevent Chemoresistance and Drug-Induced Toxicity Natural Extracts Suppress Chemoresistance Due to ROS Curcumin Resveratrol Wogonin Epigallocatechin-3-gallate (EGCG) Genistein Natural Extracts Suppress Chemoresistance Due to NF-κB Anacardic Acid Butein Cardamonin Curcumin Resveratrol Therapy-Induced Toxicity by ROS and Its Prevention by Natural Extracts Doxorubicin-Induced Cardiotoxicity Bleomycin-Induced Pulmonary Fibrosis Cisplatin-Induced Acute Kidney Injury (AKI) Paclitaxel-Induced Painful Neuropathy Cisplatin-Induced Ototoxicity Therapy-Induced Toxicity by NF-κB and Its Prevention by Natural Extracts Bleomycin-Induced Pulmonary Fibrosis Cisplatin-Induced Acute Kidney Injury (AKI) 5-Fluorouracil-Induced Intestinal Mucositis Irinotecan-Induced Intestinal Mucosal Injury Cisplatin-Induced Ototoxicity Conclusion and Future Direction References 21 Natural Compounds from Plumbago zeylanica as Complementary and Alternative Medicine Introduction Morphology and Botanical Description Phytochemistry Traditional Use of P. zeylanica Therapeutic Properties of P. zeylanica Anticancer Activity Antioxidant Activity Antibacterial Activity Antifungal Activity Antidiabetic Activity Antifertility Activity Antiviral Activity Wound Healing Activity Other Therapeutic Properties Nanobiotechnological Potential Copper Nanoparticles Silver Nanoparticles Gold Nanoparticles Conclusion References 22 Immunomodulatory Algal Metabolites for Alleviating Inflammation and Cancer Introduction Pro-Tumorigenic Inflammation Macroalgae Anti-Inflammatory Properties Red Macroalgae Anti-Inflammatory Activity Brown Macroalgae Anti-Inflammatory Activity Green Macroalgae Anti-Inflammatory Activity Macroalgae Anticancer Properties Red Macroalgae Anticancer Activity Brown Macroalgae Anticancer Activity Green Macroalgae Anticancer Activity Microalgae Anti-Inflammatory Activity Microalgae Anticancer Activity References 23 Targeting Natural Compounds to Mitochondria as a Novel Strategy for Cancer Therapy Introduction Mitochondrial Functions Role of Mitochondria in Tumorigenesis Targets Inside the Mitochondria Mitochondrial Metabolism Mitochondrial Electron Transport Chain Tricarboxylic Acid Cycle Glycolysis Mitochondrial ROS Homeostasis and Redox-Signaling Pathways Mitochondrial Dependent Intrinsic Apoptotic Signaling Pathway Induction of Apoptosis Through TP53 Epidermal Growth Factor Receptor (EGFR) Mitochondrial DNA (mtDNA) Mitochondrial Dynamics Barriers in Directing Drugs to the Mitochondria for Cancer Treatment Natural Compounds for Cancer Therapy Strategies for Mitochondria-Specific Anti-Cancer Drug Delivery Mitochondrial Targeting of Anticancer Drugs Using Delocalized Lipophilic Cations (DLCs) Targeting of Anticancer Drug Using Mitochondria-Penetrating Peptides Mitochondrial Targeting of Anticancer Drug Using Mitochondria Targeted Nano-Carriers DQAsome (DeQAlinium-Based lipoSOMES) Liposomes Polymeric Nanoparticles Inorganic Nano-Carriers Graphene Oxide Gold Nano-Carriers Mesoporous Silica Nanoparticles (MSNs) Dendrimers MITO-Porter Conclusion and Future Perspectives References 24 Recent Updates on the Bioactive Compounds of Ginger (Zingiber officinale) on Cancer: A Study with Special Emphasis of Ginge... Introduction Carcinogenesis Mechanism of Cancer Cancer: Reactive Oxygen Species (ROS) Cancer Biomarkers Medicinal Plants for the Treatment of Cancer Ginger Compounds of Ginger Anticancer Effects of Ginger Ginger-Bioactive Compound: Gingerol and Its Anticancer Effects Therapeutical Potential of Gingerol and Its Effect on Metabolic Pathways in Cancer Free Radical Scavenging and Antioxidant Activity of Gingerol Effect of Gingerol on Apoptotic Genes Effect of Gingerol on Tumor-Suppressor Genes Effect of Gingerol on Cycloxygenase Enzyme NF-B and Gingerol in Cancer Prevention Impact of Gingerol on Angiogenesis Conclusion and Future Perspectives References 25 Cytotoxic, Antitumor, and Chemopreventive Effects of Pointed Gourd (Trichosanthes dioica) Root Introduction Plant Profile: Pointed Gourd Systematics Common Names Habitat Commercial Importance Medicinal Uses Relevant Activities In Vitro Cytotoxic Effect Antimitotic Effect Antitumor Effect Cancer Chemopreventive Effect In Vitro Antioxidant Effect Discussion Conclusion References 26 Therapeutic Implications of Piperlongumine Introduction Sources of PL and Taxonomic Classification of P. longum L. Isolation and Chemical Structure Determination of PL Total Chemical Synthesis of PL Structure Activity Relationship (SAR) Studies on PL Anticancer Activities of PL Colon Cancer Lung Cancer Breast Cancer Pancreatic Cancer Renal Carcinoma Prostate Cancer Gastric Cancer Melanoma (Skin Cancer) Leukemia (Blood Cancer) PL in Combination with Other Anticancer Drugs Metabolic and Safety Profile of PL Other Therapeutic Properties Biosynthesis of PL Future Directions Conclusion References 27 Antioxidant/Pro-oxidant, Anti-inflammatory, and Immunomodulatory Effects of Thymoquinone in Cancer Prevention and Treatment Introduction Cancer Preventing Effect of TQ Antioxidant Effects of TQ in Cancer Prevention Anti-inflammatory and Immunomodulatory Effects of TQ in Cancer Prevention Anti-inflammatory Effects of TQ in Cancer Prevention Immunomodulatory Effects of TQ in Cancer Prevention Cancer Treatment Effect of TQ Pro-oxidant Activity of TQ in the Treatment of Cancer Conclusion References 28 Therapeutic Implications of Spirulina in ROS-Induced Cancer Progression Introduction What Is Spirulina? Spirulina Species, Morphology, and Taxonomy Production of Spirulina Spirulina Contents Where Spirulina Is Used? Beneficial Effects of Spirulina on Health Antitoxic, Heavy Metal Chelating Properties Hypolipidemic Hypoglycemic Effects Antimicrobial Effects Antiviral Antibacterial Probiotic Nutritional Supplement Antihypertensive In Cancer Treatment Sonodynamic and Photodynamic Therapy (PDT) in Cancer Radioprotector Effects Effects of Antioxidant and Anti-reactive Oxygen Species (ROS) ROS ROS and Cancer ROS and Cancer Progression ROS and Cytotoxic Effects Antioxidant Effects of Spirulina on Cancer Side Effects Conclusion References 29 The Role of Cannabis Species on Oxidative Stress in Cancer Cells Introduction Cannabis and Cannabinoids Cannabinoid Receptor System Application of Cannabis Species in Medicine The Endocannabinoid System Anticancer Properties and Mechanism of Cell Death Acute Versus Chronic Oxidative Stress in Cancer Genes Involved in Cancer Oxidative Stress Oxidative Stress in the Tumor Microenvironment Cannabis Derivatives and Oxidative Stress Conclusion References 30 Natural Chemopreventive Agents for the Treatment and Prevention of Oral Squamous Cell Carcinoma Introduction Ficus Species Curcumin Genistein Resveratrol Quercetin Ellagic Acid Lycopene Green Tea Bromelain Garlic and Onions Dracaena cinnabari Conclusion References 31 Phytochemicals as Pro-oxidants in Cancer Introduction Pro-oxidant Nature of Phytochemicals: Molecular Mechanisms Classification of Pro-oxidants Phytochemicals as Pro-oxidants Polyphenolic Compounds Flavonoids Carotenoids Ascorbic Acid Alpha-Tocopherol (Vitamin E) Conclusion References 32 Protective Role of Pomegranate in ROS-Induced Prostate Cancer Introduction Modulation of Inflammation and Proliferation by PJ PJ-Induced Activation of SIRT3-SOD Pathway PJ in Modulating Cell Cycle Progression PJ-Induced Modulation of NFκB Gene Expression and PJ Modulation of Cell Adhesion, Migration, and Invasion by PJ MicroRNAs, Prostate Cancer, and PJ Role of PJ in PLA2-MMP Signalling Pathway Induced Prostate Cancer In Silico Investigation of the Possible Molecular Interactions of Ellagic Acid and Urolithin A with CDK1, COX2, and NF-κB Conclusion and Future Perspectives References 33 The Effect of Oxidative Nutritional Products on Cancer Introduction Intracellular Signal Pathway of ROS in Cancer Target of ROS Modulating Cancer Natural Compounds Inhibiting GSH Pathway Natural Products Focused on the Thioredoxin Pathway Natural Products Disturbing SOD Activity Natural Products Blocking Catalase Natural Products Disturbing the NRF Pathway Vitamin Exhibiting Antioxidant and Pro-oxidant Effects Conclusions References 34 Natural Products as an Alternative Therapy for Brain Tumors Introduction Clinical Presentation Diagnosis Classification Epidemiology Risk Factors Treatment Surgical Management Upfront Management by Tumor Type Pilocytic Astrocytoma (WHO I) Diffuse Low-Grade Gliomas (WHO II) Diffuse High-Grade Gliomas (WHO III) Glioblastoma (WHO IV) Natural Products as Anticancer Agents Alkaloids as Anticancer Agents Flavonoids as Anticancer Agents Saponins as Anticancer Agents Rosmarinic Acid Cannabis and Cannabinoids Neurostatins in Brain Tumor Latex and Resins in Brain Tumors Guduchi Bittersweet in Brain Tumors Andrographolide and Brain Tumors Plumbagin in Brain Tumors Natural Products and Blood-Brain Barrier Natural Products on Cancer Stem Cells Current Status of Natural Products on On-Going Clinical Trials in TBI Conclusion References 35 Current Evidence and Future Perspectives About Herbal Therapeutics for Cancer Therapy Introduction Phytochemicals for the Treatment of ROS-Induced Cancer Tea Polyphenols Resveratrol Quercetin Curcumin Nanocarrier Based Targeted Delivery Approaches for Phytoconstituents Liposomes Dendrimers Carbon Nanotubes Polymeric Micelle Recent Developments in Analytical/Screening Techniques for the Explorative Analysis of Natural Chemopreventive Agents Extraction Techniques Liquid Chromatography-Mass Spectrometry (LC-MS) Tandem Mass Spectrometry (LC-MS/MS) Liquid Chromatography-Nuclear Magnetic Resonance Spectrometry (LC-NMR) Analysis Gas Chromatography-Mass Spectrometry Analysis (GC-MS) High-Resolution Mass Spectrometry (HRMS) Summary and Discussion Future Perspective References 36 Herbal Remedies for Improving Cancer Treatment Through Modulation of Redox Balance Introduction Redox Status in Normal Healthy Cells Redox Modulation in Cancer Cells Cancer Treatment Herbal Remedies as Adjuvants in Cancer Treatment Therapy Curcumin (Curcuma longa) Tulsi (Ocimum sanctum) Licorice (Glycyrrhiza glabra) Picrorhiza (Picrorhiza kurroa) Giloy (Tinospora cordifolia) Sweet Violet (Viola odorata) Ferulic Acid (FA) Conclusion References 37 Targeting Redox Homeostasis of Tumor Cells by Therapeutic Compounds in Cancer Introduction ROS and Cancer Cell Signaling Pathways PI3K/Akt Pathway MAPK/ERK Signaling Pathway NF-kB Pathway Medicinal Plants of Indian Origin Withania Somnifera (Ashwagandha) Aegle Marmelos Centella Asiatica Zingiber Officinale Conclusion References 38 Natural Compound-Based Nanoparticles to Target Free Radicals in Cancer Introduction Cancer Cells are Subjected to Oxidative Stress Oxidative Stress Modulates Cellular Signaling Altered Redox Is a Selective Target in Cancer Redox Chemotherapeutics Natural Product as Redox Chemotherapeutics Natural Compound-Based Nanoparticles as Redox Therapeutics Conclusion Future Prospectus References Part II: Therapeutic Implications of Synthetic Compounds 39 Small Molecule Inhibitors That Target Signal Transduction Pathways Involved in Oxidative Stress-Induced Cancer Introduction ROS and Oxidative Stress-Induced Cancer Role of ROS in Cancer Progression Role of ROS in Inducing Cancer Cell Proliferation Role of ROS in the Induction of Redox-Mediated Cellular Mechanisms Role of ROS in the Induction of Genetic Instability Role of ROS in the Induction of Tumor Hypoxia Role of ROS in the Induction of Cancer Metastasis Role of ROS in the Tumor Microenvironment Role of ROS in Cell Survival and Apoptosis Small Molecule Inhibitors Targeting ROS and ROS-Mediated Signaling Small Molecule Inhibitors Targeting Tyrosine and Serine/Threonine Kinases Small Molecule Inhibitors Targeting Proteasomes Small Molecule Inhibitors Targeting Apoptosis Concluding Remarks: Limitations and Future Perspectives of Small Molecule Inhibitors References 40 Pristimerin in Oxidative Stress and Use in Cancer Introduction Chemical Aspects of Pristimerin Cellular and Molecular Mechanisms Oxidative Stress Induction Related Cell Signaling Pathways NF-κB Signaling PI3K/Akt/mTOR Signaling MAPK Signaling Wnt/β-Catenin Signaling miRNA Metastasis, Migration, Invasion, and Angiogenesis Breast Cancer Prostate Cancer Lung Cancer Colon Cancer Melanoma Head and Neck Cancer Other Mechanisms Conclusion References 41 Polyphenolic Acetates as Potential Therapeutics and Adjuvant in Radiotherapy of Cancer Introduction Cytotoxic Effects of Polyphenolic Acetates Cell, Tissue, and Systemic Responses to Radiotherapy of Cancer Polyphenolic Acetates as Modifiers of Radiation Response Radio-Sensitization of Tumor Cells by Polyphenolic Acetates (PA) Mitigation of Acute Radiation Syndrome by DAMTC: Hematopoietic and GI Recovery Following Radiation Damage Conclusion References 42 Applications of Peptide in Cancer Therapy Introduction Why Peptides? Classification of Therapeutic Peptides AMP/Pore-Forming Peptides Cell Penetrating Peptides (CPPs) Cationic CPPs Amphipathic CPPs Hydrophobic CPPs Biomedical Applications of CPPs Tumor-Targeting Peptides (TTPs) Different Possible Options to Use Therapeutic Peptides in Cancer Treatment Peptides as Vaccine in Cancer Therapy Peptide as Radionuclide Carrier in Cancer Therapy Peptide as Cytotoxic Drug Carrier in Cancer Therapy Peptide as Hormone in Cancer Therapy Peptide as Drug in Cancer Therapy Conclusion and Future Direction References 43 The Influence of Protein Disulfide Isomerase Inhibitors on Oxidative Stress in Breast Cancer Metastasis Introduction Reactive Species in Breast Cancer Metastasis Protein Disulfide Isomerase in Breast Cancer Metastasis PDI Inhibitors as Drug Candidates for Treatment in Breast Cancer Metastasis Conclusion and Future Perspectives References 44 Beyond Natural Antioxidants in Cancer Therapy: Novel Synthetic Approaches in Harnessing Oxidative Stress Introduction Therapy and Oxidative Stress Enzyme-Related Antioxidants Glutathione (GSH) and N-Acetylcysteine (NAC) NOX Enzymes´ Inhibition NOX4 shRNA/siRNA Antioxidant Peptides Hybrid Antioxidant Compounds Antioxidant Polymers Nanoparticles Containing Inherent Antioxidant Activities Cerium Oxide (CeO2) Fullerene (C60) Platinum Nanoparticles (PtNPs) Mesoporous Silica Nanoparticles (MSNPs) Photodynamic Therapy (PDT) Chemotherapy-Associated Oxidative Stress Conclusion References 45 Arylboronic Acids and Ester-Based Prodrugs Targeting Oxidative Stress in Cancer Introduction Background Molecular Mechanism of ROS-Mediated Drug Release Prodrugs: A Challenge and Achievements Masking and De-Masking of Drugs Prodrug-Based Chemo War Against Cancer Selective Scaffolds as Arylboronic Acid (and Ester) Prodrugs Quinone Methides Nitrogen Mustard Aliphatic Nitrogen Mustard Aromatic Nitrogen Mustard Aminoferrocene-Based Arylboronic Ester Prodrug Nucleoside-Based Arylboronic Acid (Ester) Prodrugs Stilbene-Based Arylboronic Acid (Ester) Prodrug Alkaloid-Based Arylboronic Acid (Ester) Prodrugs Taxol-Based Arylboronic Acid (Ester) Prodrugs Miscellaneous Drug as Boronic Acid (Ester) Prodrug Arylboronic Acid-Ester-Based Theranostic Prodrugs Arylboronic Acid-Ester-Based Drug Delivery System Conclusion and Future Direction References 46 An Overview of Antioxidative Anticancer Therapies with Reference to the Cancer Stem Cells Introduction Oxidative Stress and Onset of Carcinogenesis Oxidative Stress and Cancer Stem Cells Oxidative Stress and Cancer Epithelial-to-Mesenchymal Transition Oxidative Stress and Tumor Cell Invasion ROS and Cancer Angiogenesis Oxidative Stress and Cancer Cell Proliferation Hypoxia and Oxidative Stress ROS-Modulated MicroRNA in Cancer Oncogene, Tumor Suppressor Gene, and Oxidative Stress Oxidative Stress and Epigenetic Modification in Cancer Tumor Microenvironment and Oxidative Stress ROS as Cancer Therapeutics Antioxidants as Preventives and Cancer Therapeutics Pro-oxidants in Cancer Therapeutics Conclusion References 47 Application of Stimuli-Responsive Polymers in Cancer Therapy Introduction Light-Responsive Polymers Temperature-Sensitive Polymers Ultrasound-Sensitive Polymers pH-Responsive Therapy Redox Responsiveness Enzyme-Responsive Polymers Magnetic Field-Responsive PMs/NPs Conclusion and Future Perspectives References 48 Evaluation of the Anticancer Activities of Isatin-Based Derivatives Introduction Isatin (1H-indole-2,3-dione/2,3-dioxindole), a Biomolecule with Biological Activity Structure of Isatin and Its Role as a Scaffold for Synthesis of Novel Anticancer Agents Isatin-Based Derivatives and Their Structure-Function Diversities Synthesis of IBDs IBDs as Kinase Inhibitors Isatin-Based Derivatives: Types and Anticancer Efficacies Isatin-Based Imines N-Substituted Isatins Isatin Dimers/Bis-Isatin Derivatives Isatin Hydrazones Isatin-Based Spiro Compounds and Spirooxindole Derivatives Isatin-Linked Chalcones/Isatin-Chalconoids Isatin-Thiosemicarbazones Isatin Conjugates/Hybrids Isatin-Based Metal Complex Ligands Multisubstituted Isatin Derivatives Redox Control of Drug (and IBDs) Action and Metabolism Redox Reactions and Pharmacological Agents Murburn Concept and Multiple Reactions of IBDs with ROS/Redox Enzymes Conclusion References 49 Efficacy of Synthetic Organic Molecule Inhibitors of TRAF2 and NCK-Interacting Kinase (TNIK) Against Colorectal Cancer Introduction Colorectal Cancer Incidence Mechanism of CRC Induction Wnt Signalling Pathway and TNIK TNIK in Wnt Signalling: A Key Pharmacological Target in CRC Cellular Kinases: Gatekeepers of Critical Cellular Processes Wnt Signalling and Oxidative Stress: A Coherent Relationship Nature of TNIK Expression in CRC Structural Basis of TNIK Catalysis and Inhibition with Reference to the Prime Kinases Assessment of TNIK Inhibitors Patterns and Quantum Chemical Basis of TNIK Inhibitors Future Directions and Challenges Conclusions References 50 Recent Advances in the Development of Synthetic Pro-oxidants: Implications for ROS-Based Cancer Therapeutics Introduction ROS Generation and Regulation Role of ROS in Cancer Prooxidant Approach for Cancer Therapy Conclusion and Future Perspectives References 51 Synthetic Small Molecules in Prostate Cancer Therapeutics Introduction Prostate Cancer Progression Current Treatments Small Molecules and Its Relevance in Targeted Therapy ETS Oncogene Targets AR Splice Variant Targets Small Molecules BRD32048 ERGi-USU VPC-18005 YK-4-279 KI-ARv-03 Conclusion References 52 Therapeutic Efficacy of Roscovitine Against Cancer Introduction Main Text Oxidative Stress and Cancer Oxidative Stress and Cell Cycle CDKs in Oxidative Stress-Induced Cancer Role of CDKs in Cell Cycle Progression CDKs in Cancer CDK Inhibitors as Potential Chemotherapeutics Drug Resistance by Tumors Plant-Based Novel Chemotherapeutic Agents Discovery, Structure, Chemistry, and Characteristic of ROSC Mechanism of Action of ROSC In vitro Anticancer Activity of ROSC In vivo Antitumor Activity of ROSC Pharmacokinetic Study and Clinical Trials of ROSC Conclusion References 53 Oxidative Stress Modulation by G-quadruplex Binder-Naphthalene Diimide Derivatives and Its Therapeutic Potential Introduction G-quadruplex Structures Present in the Telomeric Ends and Untranslated Regions of Proto-oncogenes have Regulatory Roles Oxidative Stress and Cancer Oxidative Stress Induces Perturbations in G-quadruplex Structures NDI Derivatives as G-quadruplex Ligands Conclusion References 54 A Critical Appraisal of Current Status of Synthetic Antioxidant Molecules in the Treatment of Breast Cancer Introduction Breast Cancer Epidemiology of BC Types of BC Luminal A Type Luminal B Type Triple-Negative Basal-Like HER2 Type Various Risk Factors Associated with Development of BC Role of Oxidative Stress in the Development and Progression of BC What Is Oxidative Stress? How Does ROS Formation Takes Place? Role of ROS in the Development and Progression of BC Various Signaling Mechanisms Activated/Inhibited by ROS During Development and Progression of BC (Fig. 2) Currently Available Treatment Strategies for BC by Targeting Different Signaling Mechanisms Checkpoint Inhibiting Agents Micro RNA Targeting Targeting BRCA-1 Gene Targeting P53 Protein CXCR4 Receptor Inhibiting Agents Targeting GPER Receptors Targeting P13K/Akt/mTOR Pathways Poly-ADP Ribose Polymerase (PARP) Inhibiting Agents Mitogen-Activated Protein Kinase (MAPK) Inhibiting Agents Pathway for Notch Signaling Signaling Pathway of Hedgehog/gli 1 Chimeric Antigen Receptor T-Cell (CART) Therapy Synthetic Antioxidant Molecules Under Clinical Trials for Treatment of BC Synthetic Heterocyclic Molecules for Treatment of BC Targeting Oxidative Stress Phenothiazines Flavonoids Xanthones Quinazolinones Benzofurans Dihydroquinazolinones Uracil Ebselen Pyrazolotriazine Pyrrolidinedione Chalcone Morpholine Pyrazolines Arylselenium Selenomethionine and Selenocysteine Organophosphonates Isoxazole Conclusion References Part III: Radiation and Photodynamic Approaches in ROS-Induced Cancer Therapeutics 55 Modulatory Effects of Stem Cells on Oxidative Stress and Antioxidant Defense System in Cancer Introduction Role of Oxidative Stress in Carcinogenesis Implication of Oxidative Stress in Different Stages of Carcinogenesis Effect of Different Types of Stem Cells on Oxidative Stress and ROS Production Stem Cells Stem Cell Therapy Stem Cells and Cancer Modulatory Effects of Stem Cells on Oxidative Stress and Antioxidant Defense System During Carcinogenesis and Cancer Progressi... Conclusion and Recommendations References 56 Emerging Interdisciplinary Techniques to Extend ROS Modulation for the Benefit of Chemo-/Radiotherapy in Cancer Introduction Exogenous Generation of ROS Endogenous Generation of ROS Types of ROS Free Oxygen Radicals Nonfree Radical ROS Tumor-Associated Inflammation Cellular Responses in the Form of DNA Repair Radiotherapy Direct Effects Indirect Effects Radiosensitivity and Resistance Role of Mesoporous Silica in Nanomedicine Mesoporous Silica Nanoparticle (MSN) Utility in Photodynamic Therapy (PDT) and Sonodynamic Therapy (SDT) Redox Adaptation in Cells and Its Modulation for Cancer Treatment Role of Miscellaneous Novel Small Molecular Compounds in ROS Modulation Oxamate D-Allose Histone Deacetylase Inhibitors Role of Natural Herbs in Modulating ROS in Cancer Treatment Flavonoids Polyphenols Naphthoquinones Terpenoids Ginsenosides Radiosensitization Through the Regulation of Cell Stress Responses Antioxidant System Inhibition in Cancer Cells Role of Superoxide Dismutase (SOD), an Antioxidant Enzyme, in Cancer Conclusion and Future Perspectives References 57 Photodynamic Therapy-Induced Oxidative Stress for Cancer Treatment Introduction Photosensitizers Principle of PDT and Generation of Oxidative Stress Type I Reactions Type II Reactions Singlet Oxygen (1O2) Reactions of Singlet Oxygen with Biomolecules Molecular Targets of PDT-Induced Oxidative Stress Effect of Oxidative Stress on Gene Expression PDT-Induced Cell Death Mechanisms and Signal Transduction After PDT Apoptosis Necrosis Autophagy Clinical PDT Measures to Increase Efficiency of PDT Conclusions and Future Prospects References 58 Elevating the Reactive Oxygen Species in Cancer Cells by Photodynamic Therapy Introduction to Photodynamic Therapy (PDT) Mechanism of Phototherapy Action Photosensitizing Agents Used in PDT First Generation of Photosensitizers Second Generation of Photosensitizers Third-Generation of Photosensitizers Limitations of Photosensitizers Phytochemicals Molecular Mechanism Role of Nanotechnology in PDT PDT in Different Types of Cancer PDT in Skin Cancer PDT in Esophageal Cancer PDT in Prostate Cancer Mechanism of PDT Cell Death Pathway in Different Cancers Apoptosis Autophagy Necrosis Future Perspectives References 59 Plasmonic Photothermal Therapy (PPTT) of Cancer Introduction Era of Nanotechnology Metallic Nanoparticles Metallic Nanoparticle Advantages Characteristics of Metallic Nanoparticles Ideal Properties of Nanoparticles Gold Nanoparticles (Au NPs) Silver Nanoparticles (ag NPs) Synthesis of au/ag NPs Nanotechnology in Medicine Nanotechnology in Cancer Diagnosis Plasmonics Plasmonic Photothermal Process Nanotechnology Tools Used in Cancer Diagnosis Using Gold Nanorods Using Gold Nanoshells Near-Infrared (NIR) Quantum Dots Nanotechnology in Cancer Therapy Nanotechnology as a Tool for Cancer Therapy Using Carbon Nanotubes Graphene and Graphene Oxide Polymeric Nanoparticles Conclusions References 60 Role of ROS in Combined Radiation Effect in Cancer Therapy Introduction Role of ROS to Modulate Cell Death ROS in Autophagy ROS in Apoptosis ROS in Ferroptosis ROS in Necroptosis ROS in Pyroptosis Role of ROS in Different Cancer Therapies ROS in Radiotherapy ROS in Chemotherapy ROS in Immunotherapy Effect of ROS in Combined Radiation Therapy Summary and Conclusion References 61 Application of Photodynamic Therapy for Treatment of Oral Cancer Introduction Photodynamic Therapy Brief History Basic Mechanism of PDT Components of PDT Photosensitizer Oxygen Light Sources Mechanisms of PDT-Induced Tumor Destruction Direct Cell Death PDT-Induced Damage to Tumor Vasculature PDT-Induced Inflammation and Antitumor Immunity Clinical Studies and Advantages of PDT of Oral Cancer PDT Is Noninvasive, Selective with Less Side Effects PDT as Primary, Adjuvant/Combined Modality PDT as a Palliative Treatment Modality Challenges Associated with PDT of Oral Cancer Recent Developments in PDT and Future Prospects Targeted PS Photoimmunotherapy Nanotechnology-Based Delivery Conclusion References 62 Advances in Photodynamic Protocols for Nonmelanoma Skin Cancer Nonmelanoma Skin Cancer Topical PDT in Nonmelanoma Skin Cancer Protocols Optimization for Nonmelanoma Skin Cancer Improvements of the Drug Delivery Nonmelanoma Skin Cancer and the Evolution of Topical PDT in Brazil Conclusion References 63 Metallic Core-Shell Nanoparticles as Drug Delivery Vehicles in Targeted Photodynamic Therapy of Cancer Introduction Targeted Photodynamic Therapy Basics of PDT Challenges of PDT Targeted PDT Active Targeting Passive Targeting Metallic Core-Shell Nanoparticles Preparation of Metallic CSNPs Formulations of Metallic CSNPs with Photosensitizers Characterization of CSNPs and CSNPs-PS Drug Delivery Systems Metallic CSNPs-PS in TPDT PDT Efficiency of CSNPs-PS Conjugates Subcellular Localization of CSNPs-PS Conjugates Colloidal Stability of CSNPs-PS Drug Delivery Systems in TPDT Conclusions and Future Directives References 64 Recent Advancements in Nanomaterials for Photodynamic Therapy of Cancers Introduction Principle of Photodynamic Therapy Conventional Photosensitizers and their Limitations First-Generation Photosensitizers Second-Generation Photosensitizers Third-Generation Photosensitizers Current Limitations of Photodynamic Therapy Nanoparticles in Photodynamic Therapy Nanoparticles as a Delivery Agent Biodegradable Nanoparticles Non-biodegradable Nanoparticles Active Nanoparticles Nanoparticles As Down-Converting Photosensitizers Agent Nanoparticles As up-Converting Photosensitizers Conclusion and Future Perspectives References 65 Photodynamic Therapy in Cancer Introduction Mechanism of Photodynamic Action Tumor Destruction Mechanism Direct Killing of the Tumor Cells Cell Killing Mechanisms in PDT Vascular Damage Immune and Inflammatory Response Photosensitizers First-Generation Photosensitizers Second-Generation Photosensitizers Third-Generation Photosensitizers Limitations of PDT Formulation of Photosensitizer Nanoparticles in PDT Biodegradable Nanoparticles Nonbiodegradable Nanoparticles Conclusion References 66 Radiotherapy-Induced Augmentation of Cellular Oxidative Stress Introduction Radiotherapy Types of Radiotherapy External Beam Radiation Therapy (EBRT) Conventional External Beam Radiation Therapy Intensity-Modulated Radiation Therapy (IMRT) Image-Guided Radiation Therapy (IGRT) Stereotactic Radiosurgery (SRS) Stereotactic Body Radiation Therapy (SBRT) Proton Therapy Internal Radiation Therapy How Radiation Therapy Works? Direct Effects of Radiation Types of Cell Death in Cancer Indirect Effects of Radiation Radiolysis of Water and Generation of ROS Radiation-Induced Production of Reactive Nitrogen Species (RNS) Role of Radiation in Chronic Inflammation Cellular Defenses to Handle DNA Alterations Radioprotection of Normal Cells Antioxidant Status and Radiotherapy Conclusion References 67 Photodynamic Therapy and ROS Introduction Role of PDT in Early Stages of Lung Cancer Signalling Pathways PDT Pathway Immune System Molecular Level MAPK and AKT Pathway: NF-KB Pathway Sources of ROS Detoxification from ROS ROS Effects on Tumors Conclusion and Future Perspective References Part IV: Epigenetic Tools and Gene Therapy in ROS Management: Implications in Cancer Progression 68 Oxidative Stress-Mediated miRNA Regulation in Cancer Introduction to miRNA World miRNA as a Gene Regulator miRNA-Mediated Gene Regulation Mechanism Oxidative Stress and Cancer Oxidative Stress or ROS Effect miRNA in Cancer ROS in Chromosomal Aberration ROS in Epigenetic Modification ROS in Controlling miRNA Biogenesis ROS in Regulating miRNA Functions Via Transcription Factors c-Myc P53 NF-κB HIF-1α Conclusion and Future Perspectives References 69 Reactive Oxygen Species: Induced Epigenetic Modification in the Expression Pattern of Oncogenic Proteins Introduction ROS in Cancer Development ROS Generation and Epigenetic Changes ROS and Proto-Oncogenes ROS Generation and Epigenetic Changes in TP53 ROS Generation and Epigenetic Changes in RAS ROS Generation and Epigenetic Changes in c-Myc ROS Generation and Epigenetic Changes in NF-κB ROS Generation and Epigenetic Changes in EMT Oncogenes Conclusion References 70 Targeting ROS-Induced Epigenetic Reprograming in Cancer Stem Cells Introduction Generation of ROS in Cancer Endogenous Sources of ROS in Cancer Mitochondria NADPH Oxidase Other Oxidative Organelles and Enzymes Peroxisomes Cyclooxygenases Lipoxygenases Thymidine Phosphorylase Other Oxygen Radicals Epigenetic Reprograming of CSCs and Oxidative Stress A Crosstalk Between ROS Mediated Signaling and Epigenetic Switch in CSCs as Part of Reprograming Epigenetic and Metabolic Reprograming in CSCs Conclusions and Future Directions References 71 Therapeutic Implications of Long Non-coding RNA in the Regulation of Lung Cancer Introduction lncRNAs lncRNA-Regulated Signaling Network During Lung Carcinogenesis Cell Proliferation and Apoptosis Epithelial-Mesenchymal Transition (EMT), Cell Migration and Invasion lncRNAs in Redox Regulation of Lung Cancer Therapy Resistance lncRNAs in Lung Cancer Management Biomarker in Lung Cancer Detection Downregulation of Tumor-Promoting lncRNAs by Genetic Engineering Tools Suppression of Lung Cancer-Promoting Signal by lncRNAs lncRNAs as Therapy as Well as Therapeutic Targets Major Challenges Conclusions and Future Prospects References 72 Role of Histone Methylation in Cancer: Pathobiology and Therapeutics Introduction Histone Methylation and Cancer SET Domain-Containing KMTs EZH2 MLL2 SMYD2 and SETD2 G9a and SUV39H1 SETD8 Non-set Domain-Containing KMTs KDM2A KDM3A KDM4A KDM5A KDM6A Histone Methyltransferase as New Therapeutic Target for Cancer Conclusion and Future Perspective References 73 microRNAs-Mediated Regulation of Voltage Gated Anion Channel 1: A Major Player in ROS Generation and Cancer Progression Introduction Role of microRNAs in Different Pathologies microRNA-Mediated Regulation of VDAC1 and Its Impact on Cancer Progression miR-320a and VDAC1 miR-7 and VDAC1 miR-490-3p and VDAC1 miR-197-3p and VDAC1 Prospect of microRNA Therapeutics in Cancer, Especially Targeting VDAC1 References 74 Epigenetic Regulators of NRF2 Introduction NRF2 Signaling Pathway Epigenetic Regulation of NRF2/KEAP1 in Cancer DNA Methylation Histone Modifications Histone Methylation Histone Acetylation Noncoding RNAs (ncRNAs) Potential Epi-Regulators of NRF2 in Cancer HDAC Inhibitors (HDACi) DNMT Inhibitors BET Bromodomain Inhibitors (BETi) Discussion and Conclusion References 75 Exosomal Non-coding RNAs Introduction Breast Cancer Oxidative Stress Induced Breast Cancer Exosomes Non-coding RNA in General miRNA lncRNA siRNA piRNA YRNA Exosomal Non-coding RNA and Their Sorting Mechanism General Mechanism Involved in Exosomal Sorting of ncRNAs Mechanism Involved in Oxidative Stress Induced Breast Cancer General Mechanism Mechanism Involving Exosomal ncRNAs miRNAs LncRNAs Role of Individual Exosomal Non-coding RNA in Regulating Oxidative Stress Induced Breast Cancer miRNA siRNA Exosomes Theranostics Milestones (Fig. 7) Challenges and Future Perspective/Scope Conclusion References 76 miRNA-Mediated Oxidative Stress Management in Cancer Introduction to miRNA-mediated Gene Regulation An Overview miRNA as a Regulator of Oncogenes Oxidative Stress Contribution in Cancer Oxidative Stress and Cancer Oxidative Stress Controlling in Cancer miRNA and Oxidative Stress miRNA Controlling Oxidative Stress miRNA Transport Regulation, Oxidative Stress, and Cancer Conclusion and Future Perspectives References 77 A Critical Approach in the Analysis of lncRNA Characteristics for Cancer Therapy Introduction Overview of ROS-Induced Cancers and Their Associations with lncRNAs Overview of lncRNAs Functionality of lncRNAs Biochemical Importance of lncRNAs Involvements of lncRNAs in ROS-Induced Cancers lncRNAs in Prostate Cancer PCAT-1 PCA3 PCGEM1 lncRNAs Involved in Breast Cancer HOTAIR ANRIL MALAT1 Colorectal Cancer CCAT1 Liver Cancer HULC HEIH Bladder Cancer UCA1 lncRNAs as Biomarkers and in Gene Therapy lncRNAs and Cancer Metastasis Conclusion References 78 Long Noncoding RNA Acting as Therapeutic Target for Oxidative Stress-Induced Pancreatic Cancer Introduction Treatment Strategy of Pancreatic Cancer Overview of Long Noncoding RNA (lncRNA) in Cancer Biological and Functional Roles of lncRNAs in Pancreatic Cancer Reactive Oxygen Species and Long Noncoding RNA in Cancer Long Noncoding RNA in Cancer Therapy Mediated via Oxidative Stress Long Noncoding RNA as Diagnostic and Prognostic Biomarkers for Pancreatic Cancer Long Noncoding RNAs in the Directive of Oxidative Stress, Reactive Oxygen Species and Pancreatic Cancer Progression Mechanistic Role of Hypoxia-Induced Long Noncoding RNA in Pancreatic Cancer Conclusion and Future Perspective References 79 Short Non-coding RNAs: Emerging Molecular Players in Therapeutics of ROS-Induced Cancer Introduction Short Non-coding RNAs and Cancer MicroRNAs in ROS-Induced Cancer Regulation of miRNA Expression Through ROS-Induced Transcription Factors c-Myc p53 NF-κβ HIF-1α β-Catenin and FOX Regulation of miRNA Expression Associated with ROS Through Epigenetic Modifications DNA Methyltransferases (DNMTs) Histone Deacetylases (HDACs) Modulation of miRNA Biogenesis by ROS Modulation of ROS Level by miRNAs NOX/miR-34a POX/miR-43b miR-128a miR-141/miR-200a Modulation of Mitochondrial Functions by ROS-Induced miRNAs Modulation of Antioxidants by ROS-Induced miRNAs Challenges of Using miRNAs in Therapy in ROS-Induced Cancer Small Interfering RNAs (siRNAs) in ROS-Induced Cancers siRNAs Targeting NRF2 siRNAs Targeting NOX siRNAs Targeting Romo1 siRNAs Targeting CSNK2β Piwi-Interacting RNAs (piRNAs) in ROS-Induced Cancer Small Nucleolar RNAs (snoRNAs) and Small Nuclear RNAs (snRNAs) in ROS-Induced Cancer Conclusion References 80 Implications of NRF2 in Cancer Progression and Therapeutics Introduction NRF2 Activation in Cancer Regulation of NRF2 Proteins KEAP1 Dependent NRF2 Dissociation KEAP1-Independent Regulation of NRF2 Protein Stability NRF2 Implication in Cancer NRF2 Inhibitors Brusatol Wogonin Luteolin Chrysin Apigenin Oridonin Procyanidin Trigonelline Convallatoxin Honokiol Halofuginone Parthenolide Camptothecin Conclusion References 81 Non-coding RNAs as Trojan Horse in Eliminating ROS-Induced Cancer Introduction Role of ROS in Cancer Angiogenesis Cell Proliferation Epigenetic Modification Metastasis Non-coding RNA (ncRNA) Non-coding RNAs in ROS Inhibition MicroRNAs (miRNAs) Small Interfering RNAs (siRNAs) Long Noncoding RNAs (lncRNAs) Circular RNAs (circRNAs) PIWI-Interacting RNA (piRNAs) Conclusion and Future Perspective References 82 Role of ROS-Mediated Epigenetic Alterations in the Development of Solid Tumor Introduction Role of DNA Methylation in Tumorigenesis Effect of Reactive Oxygen Species (ROS) on DNA Methylation in Tumor Cells Effect of Reactive Oxygen Species (ROS) in Tumorigenesis Effect of ROS in Regulation of Expression of MicroRNAs in Tumorigenesis Role of Epigenetic Alterations of Mitochondrial DNA in Tumorigenesis Conclusions and Perspectives References 83 Role of Notch Signalling in Oxidative Stress and Stem Cell Self-Renewal During Colitis and Colon Cancer Introduction Reactive Oxygen Species ROS, Colitis, and Colon Cancer Development of Colon Tumors Cancer Stem Cells CSCs and Colon Cancer Feedback Loop between Inflammation and Cancer Stem Cells Oxidative Stress Targets Cell Signalling Notch Signalling in Normal Intestine Notch Signalling in Colorectal Cancer Notch and Chemoresistance Wnt-Notch Crosstalk Conclusions and Future Scope Bibliography 84 Oncogenic Virus-Induced Oxidative Stress and Epigenetic Regulation: An Insight into Host DNA Methylation Introduction ROS/RNS Production Heat Stress Genotoxic Stress Hypoxic Stress Metabolic Stress Pathogenic Stress Oxidative Stress and Epigenetic Reprogramming by Oncogenic Virus Oncogenic Virus and Associated Cancers Hepatitis C Virus Hepatitis B Virus Human Papillomavirus Epstein-Barr Virus (EBV)/Human Herpesvirus 4 (HHV-4) Kaposi´s Sarcoma-Associated Herpes Virus/Human Herpesvirus 8 (HHV-8) Human T-Cell Leukemia Virus Type 1 Techniques to Identify the ROS Levels Inside the Cells Fluorescence 2D Gel Electrophoresis AP Site Assay Flow Cytometric Analysis of Cellular ROS Levels Determination of GSSG/GS Iodoacetate Tandem Mass Tag (iodoTMT) RAC-1 Activity Assay H2O2 Measurement Conclusion References 85 Radiation-Induced Epigenetic Changes and Their Modulation by Epidrugs Introduction Radiation-Induced Changes in DNA Methylation Role of DNA Methylation in Radiation-Induced Carcinogenesis Radiation-Induced Modifications in Histones Phosphorylation ADP-Ribosylation Acetylation Methylation Ubiquitination Small RNA-Mediated Alterations Modulation of Radiation-Induced Damages by Epidrugs Conclusion and Future Prospectives References 86 Mucinous Colorectal Cancer Oxidative Stress and Therapeutic MicroRNAs Introduction Types of Colorectal Cancer Colorectal Adenocarcinoma Non-mucinous Adenocarcinoma Mucinous Adenocarcinoma and Its Subtypes Major Influencers of Colorectal Cancer Loss of Heterozygosity (LOH) Microsatellite Instability (MSI) CpG Island Methylator Phenotype (CIMP) KRAS BRAF P53 and P21 Mucin Genes in Colorectal Cancer (CRC) Secreted Gel-Forming Mucins Transmembrane Mucins MicroRNAs in Mucinous Carcinoma Early Prognosis of Mucinous Carcinoma Diagnostic and Therapeutic Potential of Mucins Existing Clinical Treatments Conclusion and Future Perspectives References 87 Insights into the Oxidative Stress and microRNA-Based Therapeutics in Colorectal Cancer Introduction MicroRNA Oxidative Stress Reactive Oxygen Species(ROS) MicroRNA Biogenesis and ROS MicroRNA Regulation by ROS Through Transcriptional Factors ROS and Epigenetic Alterations Interplay or Cross Talk Between ROS and MicroRNA Associated with Cancer Cell Proliferation and Survival Programmed Cell Death Tumor Invasion and Metastasis Expression Profile of MicroRNA and ROS Levels Observed in Colorectal Cancer ROS and MicroRNA Interaction in Colon Cancer MicroRNA as a Biomarker MicroRNA in Tissues MicroRNAs in Serum or Plasma MicroRNA in Stool Pros and Cons of the MicroRNA Biomarkers ROS and MicroRNA-Mediated Therapeutic Strategies Future Perspectives and Conclusion References 88 Oxidative Stress Associated Non-coding RNAs in Pathogenesis of Urologic Cancers: Prognostic and Therapeutic Importance Introduction Oxidative Stress and Age-Related Disease Urologic Cancer, Disease Conditions Related to Oxidative Stress Non-coding RNA, a Potential Link Between Oxidative Stress and Prostate Cancer miR-21; Gene Locus, Biogenesis, and Oxidative Stress miR-21 in Prostate Carcinogenesis; a Potential Link with Oxidative Stress miR-21 vs. Cellular Antioxidant Defense miR-21 in Oxidative Stress Linked Signalling Pathways miR-21 in AR and PI3K/Akt Signalling Pathways AR Pathway PI3K/Akt Pathway Crosstalk of AR and PI3K/Akt Pathways Modulation of AR and PI3K/Akt Pathways by miR-21 miR-21 in RTK/ERK Signalling Pathway RTK/ERK Pathway RTK/ERK Pathway Modulation by miR-21 miR-21 in TGF-β Signalling Pathway TGF-β Pathway Modulation of TGF-β Signalling by miR-21 miR-21 in Cell Death Pathway Oxidative Stress and Cell Death Pathway miR-21 Suppresses Apoptosis Prognostic Importance of miR-21 in Prostate Cancer Therapeutic Importance of miR-21 in Prostate Cancer miR-21 in Predicting Efficacy of Conventional Therapy miR-21 as a Target of Novel Therapeutics Therapeutics Using Synthetic Compounds Therapeutics Using Natural Compounds Conclusion and Future Perspectives References 89 Implications of Oxidative Stress and Epigenetic Drivers in Ovarian Cancer Progression and Therapy Introduction Driver Mutations in Ovarian Cancer Progression and Treatment Oxidative Stress and Tumor Progression Role of Oxidative Stress in Ovarian Cancer Progression Epigenetics and Tumor Progression Role of Epigenetic Alterations in Ovarian Tumorigenesis Interrelationship between Oxidative Stress and Epigenetic Alterations in Ovarian Cancer Progression and Treatment Therapeutic Utilization of Epigenetic and Redox Modifiers in Ovarian Cancer Conclusion and Future Direction References 90 Noncoding RNA regulation and Oxidative Stress Introduction Noncoding RNAs (ncRNAs) Characterization of lncRNAs Characterization of Small ncRNA Oxidative Stress Sources of ROS in Cancer Cells Cellular Detoxification Systems ROS and ncRNA Expression Effect of ncRNAs on ROS Generators and Antioxidants ROS and Cancer Development Tumor Initiation Proliferation of Tumor Cells Hypoxia and Tumor Progression Resistance to Apoptosis Metabolic Reprogramming or Cellular Energetics Invasion, Metastasis, and Angiogenesis Acquisition of Cellular Stemness Conclusion References 91 MicroRNAs: The Master Regulators of the Breast Cancer Tumor Microenvironment Introduction Breast Cancer Overview Breast Cancer Subtypes Current Breast Cancer Screening miRNA Biogenesis miRNAs in Breast Cancer The TME Hypoxia and Oxidative Stress miRNAs Regulating Hallmarks of Cancer Oxidative Stress Regulating the TME Oxidative Stress and miRNAs Tumor-Associated Angiogenesis and Lymphangiogenesis Oxidative Stress and Tumor-Associated Angiogenesis Roles of miRNAs in Angiogenesis and Lymphangiogenesis in Breast Cancer CSCs and Oxidative Stress CSCs and miRNAs miRNA Therapeutic Relevance in Cancer Biomarker Capability of miRNAs in Breast Cancer Conclusion and Future Perspectives References 92 Role of MicroRNA in ROS Modulation and Its Implication in Lung Cancer and Therapeutics Introduction Sources and Regulation of ROS Intracellular Sources of ROS in Cancer ROS-Promoting Signaling Pathways ROS Regulation by Cellular Antioxidant Machinery Dual Role of ROS in Cancer Pro-tumoregenic Role of ROS Tumor-Suppressor Role of ROS MicroRNAs: Structure, Function, and Biogenesis Role of MicroRNAs (miRNAs) in Tumorigenesis Crosstalk Between miRNA and ROS in Lung Cancer Association Between miRNAs, ROS, and Deregulation of Metabolic Pathways Association Between MicroRNAs, ROS, and Hypoxia Association Between MicroRNAs, ROS, and Oncogenic Signal Transduction Pathways Association Between MicroRNA, ROS, and Antioxidant Pathways Association Between MicroRNAs, ROS, and Epithelial-to-Mesenchymal Transition Association Between MicroRNAs, ROS, and Cell Death Pathways Apoptosis Autophagy Ferroptosis Lung Cancer Therapeutics in Modulating ROS and MicroRNA Conclusion and Future Perspectives References Part V: Stem Cells in Therapeutics of ROS-Induced Cancer 93 Interplay of MicroRNAs and Reactive Oxygen Species in Cancer Stem Cells: New Perspective in Cancer Metastasis Introduction Cancer Stemness Cancer Metastasis MicroRNAs Reactive Oxygen Species miRNA Regulating ROS in Cancer Stem Cells Linked with Metastasis ROS Regulating miRNA in Cancer Stem Cells Associated with Metastasis Interplay Between ROS and miRNA in Regulating Cancer Stemness and Metastasis Conclusion and Future Direction References 94 Therapeutic Potential of Chemical Compounds in Targeting Cancer Stem Cells Introduction Impact of ROS on CSCs Endogenous Molecules Regulates ROS Signaling Pathways Wnt/β-Catenin Hh Notch TGF- β PTEN/PI3K/Akt/mTOR MAPK/ERK/STAT Transcription Factors and Genes FOXO FOXM1 Nrf2 p73 p53 NF-κB c-MYC HIF Antioxidant and Prooxidant Proteins AMPK SOD Peroxidases NADPH Oxidases (NOX) Protein Kinase C (PKC) ALDH Isocitrate Dehydrogenase (IDH) GSH Programmed Death-Ligand 1 (PD-L1) Bcl-2 Coenzyme Q10 (CoQ10) NAC Anticancer Drugs and Agents Rapamycin Amifostine Doxorubicin Paclitaxel (Taxol) Cisplatin Bevacizumab IPI-504 (Retaspimycin Hydrochloride) As2O3 Ps-341 Other Compounds and Molecules Hydroxyurea (HU) and Hydroxamic Acids (HAs) NSAIDs Arsenic (as) Selenium (se) and se Derived Compounds Taurolidine and Piperlongumine Kinase Inhibitors Photochemical Internalization (PCI) Thiol- Molecules Chloroquine Nitrones Conclusion References 95 Functional Correlation Between ROS and Cancer Stem Cells in Cancer Progression Introduction Stem Cells vs Cancer Stem Cells ROS-Induced Tumorigenesis ROS-Mediated Angiogenesis ROS-Mediated Metastasis ROS-Mediated Inflammation Hypoxia and ROS in the Maintenance of Cancer Stem Cell Pool Markers of Cancer Stem Cells and ROS Epithelial-Mesenchymal Transition (EMT) High ROS Also Contributes to EMT in CSCs Therapeutic Targeting of CSCs Conclusion and Future Perspectives References 96 Colon Cancer Stem Cells Introduction Role of Oxidative Stress in Colorectal Cancer Role of Oxidative Stress in the Formation of Colon Cancer Stem Cells Characterization of Stem Cells in the Colon Role of Stem Cells in Colon Cancer Targeting Colon CSCs in Management of Colorectal Cancer Wnt/β-Catenin Signaling Hedgehog Signaling Notch Signaling Transforming Growth Factor-β Signaling Crosstalk Among Pathways Conclusion and Future Perspectives References 97 Therapeutic Modalities Regarding ROS in Leukemia and Hematopoietic Stem/Progenitor Cell Perspective Introduction Reactive Oxygen Species (ROS): A Brief Account ROS and Mechanisms of ``Redox Homeostasis´´ Hematopoiesis: A General Overview ROS and Hematopoiesis: A Walk Through ROS and Hematological Malignancies Therapeutic Modalities Concerning ROS ROS-Modulating Therapeutic Management in Hematological Malignancy References 98 Stemness and Stromal Niche: Targets in Oxidative Stress-Induced Oral Cancer Introduction Imbalance in Generation and Elimination of Reactive Oxygen Species (ROS) Leading to Oxidative Stress in Oral Cancer Cancer Stem Cells in Oral Carcinoma and Interplay of Oxidative Stress Mechanism of Redox Balance in Maintenance of Cancer Stemness Oral Cancer Microenvironment and its Role in Maintenance of Stemness Therapeutic Options in Oxidative Stress-induced Cancer Targeting Redox Homeostasis Against Stemness Conclusion and Future Perspectives References 99 Targeting Signaling Pathways in Cancer Stem Cells for Therapy of Cancer Introduction Signaling Pathways in Cancer Stem Cells Developmental Signaling Pathway TGFβ Pathway Hippo Pathway AMPK Pathway Autophagy Properties of CSCs Regulated by Signaling Pathways Stem Cell Maintenance Tumor Microenvironment Immune Evasion Resistance to Therapy Clinical Targeting of Signaling Pathways in CSC Conclusion References 100 Cancer Stem Cell Oxidative Phosphorylation: Target for Cancer Therapy Introduction Cancer Stem Cells Metabolism Glycolysis and Cancer Oxidative Phosphorylation and Cancer Electron Transport Chain Other Roles of Mitochondria Inhibition of Oxidative Phosphorylation Inhibition of Mitochondrial Function Inhibition of Mitochondrial Transfer Inhibiting Respiratory Chain Complexes Inhibition Based on Membrane Potential Indirect Inhibition of OXPHOS Combination with Tyrosine Kinase Inhibitors and Metabolic Activities Summary and Conclusion References 101 Targeting Oxidative Stress Specific NRF2 in Pancreatic Cancer Stem Cells Introduction Overview of the Nrf2 Protein Cross Talk Between Nrf2-Keap1 Role of Nrf2 and Oxidative Stress Role of Nrf2 and Tumor Progression Role of Nrf2 and Molecular Signaling in Cancer Cancer Stem Cells Role of Nrf2 in CSCs Role of Nrf2 and Chemoresistance in CSCs Nrf2 Is a Prospective Target for CSCs Treatment Conclusion and Future Aspects References 102 Redressal of the Molecular Mechanisms of Colon and Other Cancer Stem Cell Energetics/Oxidative Stress for Possible Transla... Introduction Molecular Mechanisms of Cellular Energetics of Somatic Cells, Regenerative and Cancer Stem Cells Correlation of Cellular Energetics with the Aggressiveness of Cancer Stem Cells The Metabolic State of Cancer Stem Cells: Flexibility Versus Scarcity! Cellular Energetics of Colon Cancer Stem Cells Targeting Metabolic Regulators for CSC Eradication Targeting Metabolic Pathways with Conventional Drugs Targeting Redox Homeostasis Targeting Drug Transporters Targeting Signaling Pathways Targeting Epigenetic Modulations Conclusions and Perspectives References 103 Regenerative Medicines for ROS-Induced Cancers Treatment Introduction Inducing ROS Levels for Oxidative Stress-Induced Cell Death Suppressing Elevated Levels of ROS Stem Cells Totipotent Stem Cells Pluripotent Stem Cells Multipotent Stem Cells Unipotent Stem Cells Stem Cells Transplantation Stem Cell Use for Cancer Treatment Stem Cells Programmed for Enzyme/Prodrug Therapy Stem Cells for Viral Therapy Stem Cells as Nanoparticle (NP) Carrier for Cancer Treatment Stem Cell-Derived Exosomes Use in Cancer Therapy Stem Cells as Targeted Therapy Challenges and Risk Factors to Stem Cells Therapy Conclusion References 104 Oxidative Stress-Related Mechanisms That Mediate Chemoresistance in Cancer Stem Cells Introduction Oxidative Stress-Related Mechanisms and Chemoresistance in Hematological Neoplasias Acute Lymphocytic Leukemia (ALL) Acute Myeloid Leukemia Chronic Myeloid Leukemia (CML) Multiple Myeloma Lymphomas Cancer Stem Cell-Driven Oxidative Stress Mechanisms of Chemoresistance in Solid Tumors: Lessons from Brain and Breast Cancer Brain Tumors Breast Tumors Conclusions References 105 Cancer Stem Cells in Therapy Resistance of Colorectal Cancer Introduction Dysregulated Signaling Pathways of CSCs The Wnt/β-Catenin Signaling Pathway The Hippo/YAP Signaling Pathway The Hedgehog Signaling Pathway Other Signaling Pathways miRNA DNA Damage Repair of CSCs Maintaining Low Level of ROS Maintenance of Relative Quiescent or Dormant State Therapeutic Targeting of CSCs and Limitation of Targeting CSCs Conclusion and Future Perspective References 106 Role of Stem Cells and Reactive Oxygen Species in Cancer Introduction Stem Cell Therapy Stem Cells in Cancer Therapy ROS in Cancer ROS and Nuclear Factor Erythroid 2-Related Factor 2 (Nrf-2) Signaling Nrf-2 Signaling in MSCs Nrf-2 Signaling in Cancer Stem Cells Conclusion References 107 Therapeutic Strategies Targeting Wnt/β-Catenin Signaling Pathway in Stem Cells for ROS-Induced Cancer Progression Introduction Overview of Reactive Oxygen Species Sources of ROS Endogenous Sources of ROS Exogenous Source of ROS Wnt Signaling Pathway Regulating ROS Production ROS and DNA Damage Contribution of ROS in Stem Cell Modulation Wnt Signaling in Cancer and Stem Cells Role of Wnt Signaling Pathway and ROS Generation in Cancer ROS in Tumor Progression Apoptosis Tumor Metastasis Wnt Activators and Inhibitors Wnt Inhibitors Wnt Activators Role of Wnt Signaling in Governing Stem Cell Fate ROS and Stem Cell Fate ROS Regulation and Therapeutic Implication of Wnt Activators/Inhibitors Conclusion Future Perspectives References 108 Delineating the Role of PI3K Signaling Pathway in the Stem Cell Therapeutics of ROS-Induced Carcinomas Introduction Stem Cells: A Promising Drug Delivery Vehicle in Carcinoma Therapy Types of Stem Cells Used in Carcinoma Therapy Stem Cell Modifications in Cancer Treatments ROS-Mediated Mechanism in Cellular Processes ROS Function in Cancer Progression Source of Reactive Oxygen Species in Cancer Cells Mitochondrial ROS Role of Warburg Effect in ROS NADPH Oxidase and Xanthine Oxidase Produce ROS ER Stress and ROS ROS and Genetic Instability ROS and Cancer Crosstalk of PI3K Signaling Pathway in the Regulation of ROS Generation Therapeutic Strategies in the Regulation of ROS Mediated Cancer References 109 Therapeutic Strategies for ROS-Dependent Tumor Angiogenesis Using Vascular Stem Cells Introduction ROS-Dependent Tumor Angiogenesis Signaling Mechanisms Modulating ROS-Mediated Angiogenesis in Cancer Progression Vascular Stem Cells Types of VSCs Interplay of ROS and VSC in Tumor Angiogenesis Therapeutic Strategies Inhibition of Endogenous Production of ROS Targeting Antioxidant Enzymes MSCs: A Double-Edged Sword in Tumor Angiogenesis Perspectives and Future Direction References 110 Mesenchymal Stem Cell-Mediated Suicide Gene Therapy Introduction Suicide Gene Therapy (SGT)/ Gene Directed Enzyme Prodrug Therapy (GDEPT) Methods Involved in MSC Mediated SGT Transduction of Mesenchymal Stem Cells with Gene of Interest (GOI) Viral Methods of Transgene Delivery into MSCs Lentiviral-Based Vectors Adenoviral Vectors Adeno-Associated Virus Oncogene Retrovirus Based Vectors Non-viral Methods of Transgene Delivery into Mesenchymal Stem Cells Tissue-Specific Targeting of Genetically Engineered MSC Tumor Growth Cardiovascular Diseases Blood Neurological Disorders Enzyme/Prodrug Systems Herpes Simplex Virus Thymidine Kinase (HSV-TK)/Ganciclovir(GCV) Cytosine Deaminases (CD)/5-Fluorocytosine (5-FC) Cytochrome P450 (CYP450)/Oxazaphosphorine Clinical Studies Using MSC-Based Therapies for Cancer Treatment Future Prospects Conclusion References 111 Biopolymer-Based Nanocarriers for Stem Cells or Stem Cell Differentiating Agents and Their Therapeutic Significance Introduction Embryonic Stem Cells Very Small Embryonic-Like Stem Cells Nuclear Transfer Stem Cells Reprogramming Stem Cells Adult Stem Cells Tissue Engineering and Regenerative Medicine Tissue Engineering and Stem Cell Differentiation Regenerative Medicine and Stem Cell Differentiation Nanotechnology and Tissue Engineering Nanotechnology and Regenerative Medicine Biopolymers for Medical Applications Biopolymers for Delivery of Stem Cells Biopolymers as Carriers for Stem Cell Differentiating Agents Microtechnology 3D Printing Way Forward References 112 Reactive Oxygen Species and Cancer Stem Cells: Molecular Interactions and Their Implications in Cancer Introduction Reactive Oxygen Species and Cancer Anomalous Redox Regulation of CSCs in Cancers Role of ROS in the Transformation of Normal or Tumor Cells to CSCs ROS and CSCs in the Tumor Microenvironment ROS Act as a Vital Signal Transducer in Crucial Cell Signaling Pathways Wnt/β-Catenin Signaling Pathway Notch Signaling Pathway ATM Signaling Pathway PTEN/PI3K/AKT/mTOR Signaling Pathway JAK/STAT Signaling Pathway NFκB Signaling Pathway Contribution of ROS and CSCs to Tumor Aggressiveness Combating CSCs by Targeting ROS in Various Tumors Therapeutic Potential of Targeting the Redox Metabolism in Cancer Conclusions References 113 The Complex Interplay Between JAK-STAT Pathway and ROS in Regulating Stem Cells During Inflammation and Cancer Introduction Models of Cancer Dissemination Redox Regulation in CSCs ROS-Mediated Hypoxia Inducible Factor Stabilization in Tumor Niche Drives CSCs Inflammation Associated Mechanisms and Signalling Molecules Regulated by Immune Cells Mediate Cancer Progression and Drive CSCs The Crosstalk Between ROS, JAK-STAT Signalling, and Inflammation in CSCs Conclusion and Future Scope References 114 Emerging Metabolic Regulation of Redox Status in Cancer Stem Cells Progression and Metastasis Introduction Metabolic Plasticity and Stemness Features in CSCs Glycolytic Pathway in CSCs Role of Oxidative Phosphorylation in Regulation of CSCs Glutamine Metabolism in CSCs Lipid Metabolism in CSCs Metabolic Control by ROS and Modulation of CSCs Fate ROS-Dependent Metabolic Regulators Drive CSCs Role of HIF1α in Regulation of Redox Metabolism Role of MYC in Regulation of Redox Metabolism Role of TP53 on Regulation of Redox Metabolism Other Redox Metabolic Regulators Epithelial-to-Mesenchymal Transition and CSCs Conclusion and Future Prospective References 115 Exosomes Regulate ROS in Cancer Stem Cells Introduction Biogenesis of Exosomes Components of Exosomes Biology of Exosomes Cancer Stem Cells ROS and CSC Exosomes of CSC Exosomes and ROS Oxidative Stress and Cancer Exosome, CSC, and ROS Conclusion and Future Perspectives References 116 Photodynamic Oxidative Stress Targets Cancer as Well as Cancer Stem Cells Introduction Cancer and Cancer Stem Cells Cancer Cancer Stem Cells Reactive Oxygen Species Redox Metabolism of Cancer Cells Redox Metabolism of CSCs Redox Profile of the Tumor Mass Photodynamic Therapy Photodynamic Therapy and Cancer PDT and Its Photosensitizers PDT and ROS Photodynamic Oxidative Stress and CSCs Conclusion References 117 Adipose-Derived Stem Cells as Photodynamic Therapeutic Carriers for Treatment of Glioblastoma Exploiting Reactive Oxygen S... Introduction Glioblastoma Involvement of ROS in Cancer Progression Involvement of ROS in Glioblastoma Treatment Adult Stem Cells and ADSCs Using Stem Cells in Cancer Treatment Using ADSCs as Delivery Vehicles for Anticancer Drugs ADSCs Used as a Post-Cancer Treatment Regenerative Tool Photodynamic Therapy Photodynamic Therapy and Reactive Oxygen Species Photodynamic Therapy Treatment for Glioblastoma ADSCs as a PS Drug Carrier for Treating Glioblastoma Discussion Conclusion References 118 Targeting the Metabolism in Cancer Cells for Cancer Therapy Introduction Cellular Sources of ROS Generation and Their Metabolic Detoxification ROS as a Volatile Inducer of Cancer Metabolic Pathways, ROS, and Redox Homeostasis Glycolysis and Oxidative Phosphorylation Pentose Phosphate Pathway Glutamine Metabolism Targeting the Reprogrammed Cancer Cell Metabolism and Its Redox Reactions for Cancer Therapy Targeting the Cancer Cell Metabolism and Its Redox Reactions Using Small Molecules for Clinical Advancements in Cancer Therapy Conclusions References 119 Cancer Stem Cells: Reactive Oxygen Species-Induced Drug Resistance in Cancer Introduction Cancer Stem Cells Properties of CSCs Functions of CSCs Therapy Resistance by CSCs Reactive Oxygen Species Cellular Sources of ROS Cellular Detoxification of ROS Signaling Pathways Regulated by ROS in Cancer ROS-Mediated Regulation of the MAPK Pathway Oxidative Stress Regulation of the PI3K/Akt Pathway ROS Regulation of the IKK/NF-κB Pathway Specific Functions of ROS in Cancer Cancer Metastasis and ROS Angiogenesis and ROS ROS in Tumor Cell Proliferation ROS-Mediated Apoptosis and Cell Survival ROS and the Mitochondrial Pathway ROS and the Death Receptor Pathway ROS and Redox Regulation in CSCs ROS-Related miRNAs in CSCs ROS: Drug Resistance Antioxidant Mechanisms and ROS-Related Markers in CSCs p38 MAPK Pathway Aldehyde Dehydrogenases CD44 CD13 ABCG2 Transporter ROS and Antioxidants in Cancer Therapy and Prevention Conclusion References 120 Reactive Oxygen Species in Oral Squamous Cell Carcinoma Progression and Importance of Stem Cells in Cancer Therapeutics Introduction Reactive Oxygen Species (ROS) ROS in Cancer Oral Squamous Cell Carcinoma Impact of ROS in Oral Squamous Cell Carcinoma Initiation and Progression ROS in Oral Cancer Stem Cells ROS-Based Anti-cancer Therapy Cancer Stem Cells in Squamous Cell Carcinoma and Therapy ROS-Based Stem Cell Therapy in Oral Cancer Conclusions References 121 Regulation of ROS in Skin Stem Cells for Cancer Therapeutics Introduction Reactive Oxygen Species (ROS) Skin Cancer: An Overview Common Treatment Strategies for Skin Cancer Surgery Radiation Therapy Chemotherapy Immunotherapy Photodynamic Therapy Targeted Therapy Stem Cell Cancer Stem Cell and Normal Stem Cell Properties of Cancer Stem Cells Recent Strategies to Target Cancer Stem Cells Cancer Stem Cells and Reactive Oxygen Species Anti-oxidants in Cancer Prevention and Treatment Manganese Superoxide Dismutase (MnSOD) and Its Clinical Application in Skin Cancer Skin Cancer Chemoprevention: Role of Nicotinamide Melatonin and Its Anti-tumor Effects Phytochemicals in the Treatment of Skin Cancer Polyphenols Regulating Oxidative Stress in Skin Cancer Flavonoid (Luteolin) Against Skin Cancer Photodynamic Therapy (PDT) in Skin Cancer Treatment Targeting Cancer Stem Cells to Treat Skin Cancer Stem Cells in Regenerative Medicine Summary References 122 Modulation of Reactive Oxygen Species and Cancer Stemness by Catechins Introduction Bioavailability and Metabolism of Catechins Antioxidant Potential of Catechins Anticancer Properties of Catechins: Targeting Human Cancer Stem Cells EGCG: The Cancer Stemness Markers and NFKB Signaling Pathway Green Tea Prevents Cancer Conclusions References 123 Mesenchymal Stem Cells Introduction Cancer Epidemiology Current Challenges in Cancer Treatment Components of the TME Role of MSCs in the TME Anticancer Therapeutic Potential of MSCs Conclusion and Future Perspective References 124 Induction of Oxidative Stress: A Promising Approach in Female Gynecological Cancer Therapeutic Arsenal Introduction OS Involvement in Ovarian Physiology and Malignancy Redox State in Ovarian Carcinoma Redox State in Chemoresistant Ovarian Carcinoma OS-Based Therapies in OC Antioxidant Role of Metformin in OC Treatment Endometrial Carcinogenesis and OS Involvement Antioxidant Role of Metformin in Endometrial Cancer Treatment Antioxidant Role of Phytochemicals in Endometrial Cancer Treatment OS Involvement in Cervical Carcinogenesis Antioxidant Role of Curcumin in Cervical Cancer Treatment Antioxidant Role of Metformin in Cervical Cancer Treatment Conclusions References 125 Iron Vulnerability of Cancer Stem Cells Introduction Iron as a Central Player and Essential Target in Cancer Progression Iron Metabolism in Non-CSCs and CSCs Iron-Mediated Lipid Peroxidation and Cancer Cell Death Iron-Mediated Lipid ROS Generation and Ferroptosis in CSCs Ferroptotic Nexus with Other Forms of Cell Death in Cancer Ferroptosis and Apoptosis: Synergism or Antagonism Autophagy Degrades Ferritin to Facilitate Ferroptosis Small Molecule Lipid ROS Modulators and Their Role in Induction of Ferroptosis in CSCs Erastin RSL3 Fin56 FINO2 Salinomycin and Its Derivatives Molecular and Metabolic Pathways Regulating Iron Mediated Cell Death-Ferroptosis The Transsulfuration Pathway The Mevalonate Pathway SLC7A11 and Its Vital Role in Ferroptosis Ferroptosis Inhibition by GPX4 Role of ACSL4 in Ferroptosis Role of FSP-1 in Ferroptosis Regulation of Ferroptosis by p53 NRF2/NFE2L2-Mediated Ferroptosis Hippo Signaling Pathway and Its Role in Inhibiting Ferroptosis Conclusion and Future Perspectives References 126 Targeting Epithelial-to-Mesenchymal Transition for Breast Cancer Stem Cells Therapeutics Introduction Epithelial-to-Mesenchymal Transition (EMT) and Breast Cancer Stem Cells (CSCs) In Silico Analysis of EMT Genes in Breast CSCs Preclinical Evaluation of Therapeutics Against EMT in Breast Cancer Clinical Trials of Candidate Drugs Against EMT in Breast Cancer Reversing EMT in Metastatic Breast Cancer Stem Cells Conclusion and Future Perspectives References 127 ROS Signaling in Brain Tumor Introduction Reactive Oxygen Species and Stem Cells Brain Tumors Brain Tumor Stem Cells Current Brain Tumor Treatment Modalities Involving ROS ROS Modulation in Brain Tumor Stem Cells for Therapeutic Intervention Future Perspective References 128 Current Insights to Therapeutic Targets of ROS-Induced Gastric Cancer Stem Cells Introduction Classification of Gastric Cancer Histological Basis Adenocarcinoma Lymphoma Gastrointestinal Stromal Tumor (GIST) Gastrointestinal Carcinoid Tumor Other Cancers Molecular Basis The Cancer Genome Atlas (TCGA) Subtypes The Asian Cancer Research Group Stem Cells in the Stomach Reactive Oxygen Species in Gastric Cancer Role of Reactive Oxygen Species and Helicobacter Pylori in Gastric Cancer Gastric Cancer Stem Cells Markers of GCSC ROS and Gastric Cancer Stem Cell Current GC Treatment and Prospects for Targeting GCSC Prospects for Gastric Cancer Treatment by Targeting ROS Conclusion References 129 Clinical Approaches in Targeting ROS-Induced Cancer Introduction Therapies Drug-Based Therapies Immunotherapy Photoimmunotherapy (PIT) Tumor-Infiltrating Lymphocytes (TIL) CAR T-Therapy Monoclonal Antibodies (mAbs) Photodynamic Therapy (PDT) Sonodynamic Therapy (SDT) Hydrogen Gas Therapy HSP90 Inhibitors Mn Porphyrins Vaccines Hematopoietic Stem Cells (HSC) Therapy Immunosenescence Conclusion References 130 ROS-Induced Cancers Introduction Oxidative Stress - Implications of ROS in Cancer Generation of ROS Effects of ROS - Two Opposing Actions on Cancer Cells ROS in Favor of Oncogenesis ROS Can Destroy Cancer Cells ROS in Cancer Therapy Chemotherapy Radiotherapy Surgery Targeting ROS in Glioma and Other Cancers: Implication of Combinatorial Approach Erythroid 2-Related Factor 2 (Nrf2) Cannabidiol (CBD) Deoxy-Podophyllotoxin (DPT) Bevacizumav Nanotherapy Is the Best Choice for Targeting ROS in Glioma and Other Cancers Cerium Oxide Nanoparticles (CNP) Nanoceria Conclusion References 131 An Insight into Targeted Therapy for Ovarian Cancer Introduction Targeted Therapies Homologous Recombination and PARP Inhibitors in OC Therapeutics VEGF/VEGFR-Mediated Angiogenesis PI3K/AKT/mTOR Pathway Cyclin-Dependent Kinases (CDKs) MAPK Pathway SRC Family Kinases Folate Receptor Alpha p53 Pathway Immunotherapy MicroRNA-Based Therapeutics Combination Therapy Conclusion References Part VI: Nanotechnology-Based Therapeutics of ROS-Induced Cancer 132 The Multifaceted Function of Nanoparticles in Modulating Oxidative Stress in Cancer Therapy Introduction Application of Antioxidant Nanoparticles in Therapeutic Approaches Antioxidants Nano-antioxidants Function of Nanoparticles as Antioxidant Protective Activity of Nanoparticles Against Induced Oxidative Stress in Normal Cells Mechanism of Nanoparticles to Induce Oxidative Stress and Toxicity in Cancer Cells Generation of ROS DNA Damage Source of Nanomaterials and Their Impact on Cytotoxicity and Oxidative Stress Metal Nanoparticles Nonmetal Nanoparticles Detection of Oxidative Stress in Cancer Cells Through Nanoparticle-Based Sensors Conclusion References 133 Selenium Nanoparticle in the Management of Oxidative Stress During Cancer Chemotherapy Introduction Cancer and Stages of Carcinogenesis Insight into the Role of Reactive Oxygen Species in Cancer Different Aspects of Cancer Chemotherapy Selenium and Its Efficacy Development of Nano Selenium for Application in the Field of Cancer Nano Selenium in Combination with Antineoplastic Drugs for Cancer Therapy Differently Functionalized/Decorated Nano Selenium with Anticancer Drugs in Cancer Therapy Organo Diselenide Nano Composite as the Carrier of Cancer Chemotherapeutic Drugs Conclusion and Future Direction References 134 Emerging Role of Redox-Active Nanoceria in Cancer Therapeutics via Oxidative Stress Introduction Anticancer Activity of CeO2NPs Colon Cancer Breast Cancer Lung Cancer Cervical Cancer Ovarian Cancer Liver Cancer Skin Cancer Prostate Cancer Gastric Cancer Bone Cancer Neuroblastoma Fibrosarcoma Drug Delivery Application of CeO2NPs Conclusion and Future Perspectives References 135 Nanotechnology in ROS-induced Cancer Therapy Introduction What Is Reactive Oxygen Species Promotion of Cancer by Oxidative Stress and Expose the Achilles Heel ROS: A Double-edged Sword Role of ROS in Cancer Cell Killing Cellular Apoptosis and ROS Autophagy and ROS Anticancer Therapy and ROS Antioxidant System Inhibition Within Cancerous Cells ROS Production in Cancerous Cells miRNAs and ROS ROS-mediated Cancer Cell Killing via Nanoparticles Antioxidant-mediated Cancer Cell Killing Through Dietary Phytochemicals Role of Different Nanomaterials (NPs) in Cancer Treatment Organic Nanomaterials in Cancer Therapies Polymeric Micelles (PMs) Polymeric Nanoparticles Liposome Dendrimers Inorganic Nanoparticle Silica Nanoparticles Nanographene Gold Nanoparticles (AuNPs) Quantum Dots (QDs) Conclusion and Future Perspective References 136 Nanotechnology-Based ROS-Triggered Therapeutic Strategies in Multiple Cancer Introduction Reactive Oxygen Species Oxidative Stress: ``A Necessary Evil´´ in Cancer Pathogenesis Nanoparticle-Mediated ROS Generation in Cancer Therapy ROS-Inducing Strategy of NPs Photodynamic Therapy Sonodynamic Therapy Microdynamic Therapy Ferroptotic Therapy Gas Therapy Reports on NP-Mediated Enhanced Target Specificity and Reduction in Side Effects of Different Sensitizers ROS-Mediated Tumor Cytotoxicity by Nanoparticles Metal and Metal Oxide NPs Silver NPs Magnetic NPs Selenium NPs Cadmium Quantum Dots Zinc Oxide NPs TiO2 NPs Nickel Oxide Cerium Oxide NPs Some Other NPs Graphene Oxide NPs Protein NPs Limitations Associated with Metal-Metal Oxide NPs in Cancer Therapy Nanocarriers Used in Commercially Available ROS Generating Chemotherapeutics Conclusion References 137 Nanotechnology in Cancer Diagnosis and Therapy Introduction Nanotechnology in Drug Delivery and Cancer Therapy General Means of Nanoparticle-Based Targeted Drug Delivery Passive and Active Targeting Stimuli-Responsive Drug Targeting and Triggered Release System Nano-formulations in Cancer Therapy Nanotechnology in Cancer Immunotherapy Nanotechnology in Cancer Diagnosis Challenges and Future Prospects Conclusion References 138 Biogenic Nanomaterials Derived ROS for Cancer Therapy Introduction Biogenic Nanoparticles Biogenic Synthesis of Nanoparticles Reactive Oxygen Species Based Cancer Therapy Redox Homeostasis by Nanoparticles Biogenic Nanoparticles for Redox-Based Cancer Immunotherapy PLGA Biogenic Nanoparticles Liposomes Biogenic Nanoparticles Cerium Oxide Nanoparticles Paramagnetic Iron Oxide Nanoparticles Gold Nanoparticles Iron Oxide Nanoparticles Carbon Nanoparticles Nanoparticles Induced ROS Generation to Alter Biological Functions Nanoparticles Induced DNA Damage ROS Mediated Combinatorial Nanoparticle for Anticancer Therapy Conclusions References 139 Emerging Nano-selenium: An insight to Its Current Status and Potentials in ROS-Induced Cancer Prevention and Therapy Introduction Reactive Oxygen Species and Carcinogenesis Selenium Nanoparticles (Se-NPs) and Its Importance Immense Role of Selenoproteins in the Pharmacological Activity of Se-NPs Se-NPs as Prooxidant Se-NPs as Antioxidants Se-NPs as Anticarcinogenic Se-NPS as Antimicrobial Agent Conclusion References 140 Oxidative Stress-Dependent Anticancer Potentiality of Nanotherapeutic Zinc Oxide Introduction Importance of Nanotechnology in Biomedical Research Reason for Considering ZnO NPs in Anticancer Therapy Synthesis Techniques of ZnO NPs Chemical Coprecipitation Sol-Gel Method Solution-Free Mechanochemical Method Ultrasonication Solid-State Pyrolytic Method Biological Methods Brief Insight into the Mechanism of ZnO NP Internalization Mechanism of ZnO NP-Imposed Anticancer Effects ZnO NPs and Apoptosis Zinc-Driven Altered Protein Activity ROS Generation and Oxidative Stress Induction ROS-Induced DNA Damage and Subsequent Apoptosis ZnO NPs and Autophagy ZnO NPs and Inflammation ZnO NPs as Vehicle of Chemotherapeutic Drug Delivery The Role of ZnO NPs in Drug Delivery System Conclusion References 141 Polymeric Nanoparticle-Encapsulated Curcumin: A Preventive Strategy in ROS-Induced Carcinogenesis Introduction Role of Reactive Oxygen Species (ROS) on Carcinogenesis Polymeric Nanoparticle-Encapsulated Curcumin and Its Importance Polymeric Nanoparticle-Encapsulated Curcumin as Antioxidant Polymeric Nanoparticle-Encapsulated Curcumin as Antioxidant and as Anticarcinogenic Polymeric Nanoparticle-Encapsulated Curcumin as Antioxidant and as Antimicrobial Agent Conclusion References 142 EPR-Selective Biodegradable Polymer-Based Nanoparticles for Modulating ROS in the Management of Cervical Cancer Introduction Main Text Introduction Cervical Cancer vs ROS Role of ROS in Cervical Cancer Progression Role of ROS in Cervical Cancer Therapy Resistance Role of ROS in Cancer Cell Destruction Biodegradable Polymer-Based Nanoparticles for Enhanced Permeability and Retention Polymers as Targeting Moieties Polymers as Drug Delivery Carriers Relation Between Biodegradable Polymers with ROS ROS-Based Solubility Switch ROS-Based Bond Cleavage Other ROS-Based Mechanism ROS-Regulated Signal Pathway and Oxidative Stress in Cancer Promotion Nuclear Factor-Kappa B Signaling Pathway MAPK/ERK Pathway Oxidative Stress Regulation of the PI3K/AKT Pathway EGFR/VEGFR Signaling Pathway Apoptotic Signaling Pathways Biodegradable Polymer in Modulation of ROS Thermo-responsive Polymer pH-Responsive Polymers ROS-Responsive Polymers H2O2-Responsive Polymer Light-Triggered Polymers Prospects Conclusion References 143 Graphene-Based Nanomaterials for ROS-Mediated Cancer Therapeutics Introduction Background of Graphene-Based Nanomaterials Historical Background Synthesis Graphene Nanomaterials Reactive Oxygen Species Background of ROS Sources of ROS Molecular Targets of ROS Role of ROS in Cancer Therapeutics Therapeutic Applications of Graphene Based Nanomaterials Graphene Oxide (GO) Reduced Graphene Oxide (rGO) Graphene Quantum Dots Graphene Scaffolds Mechanism of Action of Graphene Based Nanomaterials Toxicity of Graphene Based Nanomaterials Challenges and Future Perspectives Conclusion References 144 Bio-inspired Protein-Based Nanoparticles in Cancer Therapy Introduction Cancer Therapy Synthesis of Protein-Based Nanoparticles Chemical Methods Emulsion Coacervation Physical Methods Nano-Spray Drying Electro Spray Self-Assembly Methods Self-Assembly Desolvation Protein Nanoparticles for Cancer Therapy Albumin-Based Nanoparticles Gelatin-Based Nanoparticles Transferrin-Based Nanoparticles Ferritin-Based Nanoparticles Gliadin-Based Nanoparticles Silk Fibroin-Based Nanoparticles Zein Based Nanoparicles Lipoprotein-Based Nanoparticles Other Proteins-Based Nanoparticles Conclusion and Future Perspectives References 145 ROS-Responsive Bioconjugate Nanoparticles in Cancer Treatment Introduction ROS, Fenton Reaction, and Cancer Tumor Targeting Strategies Targeting Cancer Tumors Based on Their Distinguished Pathophysiology Targeting Cancer Tumors Based on the Special Properties of NDDS Bioconjugation Strategies ROS Induction for Cancer Treatment Using Bioconjugates ROS-Mediated Drug Release via Bioconjugates Thioketal Linkers Arylboronic Esters Linkers Diselenide Linkers Mesoporous System Conclusion and Future Perspectives References 146 Harnessing Microenvironment Variation for Nanotechnology-Based Therapeutics of ROS-Induced Cancer Introduction Section 1: ROS in Mediating Drug Delivery Using ROS-Responsive Drug Delivery Nanocarriers with ROS-Induced Solubility Change Nanocarriers with ROS-Induced Cleavage Section 2: Effect of Tumor Microenvironment on ROS-Responsive DDS Normalization of High Interstitial Fluid Pressure (IFP) Reduction of the Pericyte Coverage Reducing the Extracellular Matrix Components Modulating Tumor Vascularization Tumor-Associated Fibroblast (TAF) Depletion Conclusion and Future Perspective References 147 Experimental Animal Models to Evaluate the Therapeutic Efficacy of Nanoformulations Against Cancer Introduction Drug Design and Formulation Cancer Nanotechnology for Cancer Management Nanoparticles as Drug Delivery Systems in Cancer Treatment Nanoparticles as Diagnostic Systems in Cancer Treatment Biopolymers Biopolymer Nanoparticle Preparation Biopolymer Nanoparticle Biomedical Applications Biopolymers Carrying Anticancer Drugs Biopolymers and Antioxidant Property Experimental Animal Models Small Animal Models for Understanding the Efficacy of Nanocarriers Large Animal Models for Understanding the Efficacy of Nanocarriers Xenograft Experimental Models for Understanding the Efficacy of Nanocarriers Genetically Engineered Models for Understanding the Efficacy of Nanocarriers Chemically Induced Animal Models for Understanding the Efficacy of Nanocarriers Zebrafish Model for Understanding the Efficacy of Nanocarriers Cell Line-Induced Cancer Model for Understanding the Efficacy of Nanocarriers Drosophila Model for Understanding the Efficacy of Nanocarriers Conclusion and Way Forward References 148 Nanotechnologies in Oncology Introduction Cancer Conventional Treatments Multidrug Resistance Nanotechnologies in Oncology Nano-oncology How Nanotechnology Can Improve Cancer Treatment Active vs Passive Delivery Drug Release and Targeting Diagnostics (Early Detection) Types of Nanoparticles Used in Nano-oncology Inorganic/Metallic Nanoparticles Silver Nanoparticles Gold Nanoparticles (Au NPs) Magnetic Nanoparticles Platinum Nanoparticles (Pt NPs) Quantum Dots (QDs) Carbon Nanotubes (CNTs) Organic Nanoparticles Liposomes Polymers Micelles Dendrimers Hydrogels Biological Nanoparticles Nanobodies (NBs) Protein-Drug Conjugated NPs Extracellular Vesicles (EVs) Recent Developments in Nano-oncology Challenges and Future Prospects Regulatory Issues Physiochemical Characterization Toxicology Large-Scale Production Conclusions References 149 A Detailed Overview of ROS-Modulating Approaches in Cancer Treatment Background Role of Reactive Oxygen Species (ROS) in Normal Healthy and Cancer Cells Role of ROS in Normal Cells Reactive Oxygen Species Role in Cancer Cells Cancer Treatment: ROS-Modulated Therapeutic Approaches ROS Scavenging Anticancer Approaches (Antioxidant Therapy) ROS-Promoting Therapy (Prooxidant Therapy) Need for Targeted Nanosystem Approach Delivery for Prooxidant Therapy Nanoparticles as Passive Agent: Drug Carrier Nanoparticles as Active Agent: Drug Carrier Cum PDT Agent Conclusion References 150 Nanotechnology-Based Therapeutics in ROS-Induced Cancer Introduction Oxidative Stress and Carcinogenesis Advantages of Nanomedicine Nanoparticles Targeting Mechanisms Nanoparticles-Induced Oxidative Stress Nanoparticles as Drug Delivery System Redox-Responsive Systems ROS- and GSH-Responsive Nanoparticles Regulating and Manipulating Antioxidants Organic NPs Inorganic NPs Hybrid NPs Targets of ROS-Induced Cancer Therapy Internal Stimuli Targets External Stimuli Targets Temperature Stimuli-Responsive Systems Photo-/Light-Responsive Systems Magnetic-Responsive Systems Ultrasound-Responsive Systems Conclusions References 151 Recent Developments in ROS-Based Nanotherapeutic Modalities in Preclinical Cancer Treatment Introduction ROS-Based Cancer Nanotherapeutics Photodynamic Therapy (PDT) Sonodynamic Therapy (SDT) Radiation Therapy (RT) Chemodynamic Therapy (CDT) Controlled Drug Release (CDR) Synergistic Therapy PDT-Based Synergistic Therapy SDT-Based Synergistic Therapy RT-Based Synergistic Therapy CDT-Based Synergistic Therapy Conclusions and Outlook References 152 Free Radical Chemistry of Carotenoids and Oxidative Stress Physiology of Cancer Introduction Structural Properties of Carotenoids Chemical Properties of the Major Carotenoids Carotenoids as Antioxidants Carotenoids as Anticancer Molecules in the Perspective of Free Radical Chemistry Carotenoids and Their Synergism on Oxidative Stress-Mediated Apoptosis Role of Carotenoid Oxidation Products/Isomers/Metabolites in Cancer Cells Chemical Biology Approach Through Synthetic Chemistry Deciphering the Mechanism of Action Conclusion References 153 Targeting Redox Homeostasis in Tumor Cells Using Nanoparticles Introduction Biology of ROS Productions and Its Outcome Importance of Redox Homeostasis in Cancer Therapy Nanoparticles for Mediating Redox Imbalance and ROS Generation in Cancer Inorganic Nanoparticles for Altered Redox Homeostasis Organic Polymer Nanoparticles and Carbon Nanostructures for Redox Stress NP Mediated Photodynamic Therapy-Induced ROS Production Mechanisms of NPs Mediated ROS Toxicity and Disruption of Redox Homeostasis in Cancer Cell Conclusion and Future Direction References 154 In Silico Analysis of Oxidative Stress Gene Expression Profile and Biomarker Detection Introduction Anti-oxidative Stress Gene Profiling Thioredoxin Pathway Glutathione Pathway BioProfiling.de Portal Biomarker in Oxidative Stress miRNA miRNA Target Identification Tools TargetScan DIANA-microT-CDS PicTar Algorithm miRanda Algorithm RNAhybrid Algorithm DNA Methylation Analysis Bioinformatics Tools for Detection of DNA Methylation Data DNA Methylation Databases CpG Islands Detection Tools Conclusion Bioinformatics Analysis Case Study 1 (Fig. 1) Case Study 2 (Fig. 2) References 155 Nanomedicines for Tumor-Associated Macrophages Introduction Therapeutic Modalities to Target TAMs Developing Nanomedicines Against TAMs TAM-Specific Nanocarriers Polymeric Nanoparticles Liposomal Nanoparticles Inorganic Nanoparticles Carbon-Based Nanoparticles Functionalization of Nanocarriers to Target TAMs Carbohydrates as Targeting Motifs Proteins/Peptides as Targeting Motifs Effector Molecules Conjugated to Nanocarriers Limitations of TAM-Specific Nanotherapy and Its Future Conclusion References 156 Synthetic Migrastatic: A New Class of Anticancer Drug Introduction Metastasis Modality Main Text Current Therapeutic Regime and Problems Migrastatics: A New Class of Drugs Potential Targets for Migrastatic Compounds Cytoskeletal Proteins Actin-Related Proteins Focal Adhesion Complex Protein Enzymes and Signaling Protein Migration-Specific Small GTPase Potential Migrastatic Compounds Myosin Inhibitor Arp2/3 Inhibitor Tropomycin Inhibitor Inhibitors of Rho-Kinase (ROCK) Actin Filament-Related Inhibitor MLCK Inhibitor Protein Enzyme Inhibitor Probable Problems with Migrastatic Candidates as Anticancer Drugs Future Perspective and Conclusion References 157 Targeting Reactive Oxygen Species (ROS) for Cancer Therapy Introduction How ROS and Oxidative Stress Are Interlinked? ROS Signaling in Cancer Biology How ROS Severe the Metastasis? ROS as a Cancer Therapy How Low ROS Prevent Cancer Progression? Toxic ROS as Therapy for Cancer Treatments Mitochondria: The Novel Targets for ROS in Cancer Treatment Crosstalk Between Autophagy and Apoptosis-Targeting ROS Mathematical Modeling for Selecting Appropriate ROS Therapy ROS Detection in Cancer Treatments Conclusion References Part VII: Bioinformatics and System Biology Approach for Targeting ROS in Cancer Therapy 158 Elucidation of Possible Role of Heat Shock Protein as Potent Therapeutic Agent in ROS-Mediated Cancer and Its Assessment T... Introduction Origin of ROS ROS-Regulated Signal Pathways in Cancer ROS in Advancement of Tumor Cells Personification of HSP in Cancer Ontogeny Role of HSP27 in Cancer Progression Functional Activity of HSP60 in Cancer Prognosis Execution of HSP70 in Cancer Augmentation Role of HSP90 in Cancer Advancement Function of HSF1 in Cancer Prognosis Pointing HSP40 Marking HSP60 Targeting HSP70 Targeting HSP90 in Cancer The Computational Approach: An In Silico Methodology High-Throughput Data Analysis and Bibliographic Analysis Differential Gene Expression and Correlation Analysis Structural Analysis by Targeting Small Heat Shock Proteins as Potential Candidates in Therapeutic Studies Network and Pathway Enrichment Analysis Conclusion References 159 An Overview of In Silico Drug Discovery with Emphasis on Cancer Introduction Overview of Different Computational Methods Quantitative Structure Activity Relationship (QSAR) Classification of the QSAR Methods Limitations of Classical Quantitative Structure Activity Relationship Three-Dimensional Quantitative Structure Activity Relationship Overview of ROS-Induced Cancer Application of Quantitative Structure Activity Relationship in Drug Development A Few Success Stories Conclusion References 160 Application of Bioinformatics Databases in the Study of Oxidative Stress Related Cancers Introduction Essential Aspects of Reactive Oxygen Species (ROS) Interrelation Between Reactive Oxygen Species (ROS) and Cancer Anticancer Strategies Importance of Bioinformatics Biological Databases RedoxiBase: A Database for ROS Homeostasis Regulated Proteins (https://peroxibase.toulouse.inra.fr) COSMIC: Catalogue of Somatic Mutations in Cancer (https://cancer.sanger.ac.uk) ONCOMINE: A Cancer Microarray Database (https://www.oncomine.org) miRCancer: A MicroRNA-Cancer Association Database (http://mircancer.ecu.edu) Lnc2Cancer: A Manually Curated Database of Experimentally Supported lncRNAs Associated with Various Human Cancers (http://bio-... The Cancer Genome Atlas (http://cancergenome.nih.gov/) canSAR (https://cansarblack.icr.ac.uk/) MethyCancer (http://methycancer.psych.ac.cn/) miRCancer (http://mircancer.ecu.edu/) Network of Cancer Genes (http://ncg.kcl.ac.uk/) Biological Databases, Bioinformatics, and Their Roles in Cancer Therapy Conclusion References 161 Emerging Scope of Computer-Aided Drug Design in Targeting ROS in Cancer Therapy Introduction ROS-Based Targets/Pathways for Screening Application of Modeling Methods for ROS ROS In Vitro Estimation Modeling Approaches and Classification Applicability of In Silico Modeling to Study ROS Biology Software Tools for Modeling ROS Biology Limitations of Mathematical Modeling Integration of ROS Modeling with Omics Data Omics Databases Computer-Aided Drug Design: A Pipeline for Converting Structure Biology Data into the Forecasting of Drug Therapies Conclusion References 162 ROS Modulatory Role of HDAC Inhibitors in Cancer Cells Introduction HDAC Inhibitors and ROS Production HDAC Inhibitors and Protein Quality Control Systems Molecular Chaperons Ubiquitin Proteasome System Autophagy Endogenous ROS Activation Thioredoxin Role in ROS Regulation Glutathione Role in Antioxidation Reactive Oxygen Species: Types, Source, and Detoxification ROS in Normal, Cancer, and Cancer Stem Cells ROS Production ROS in Cancer and Role of Signaling Pathways Foxo Protein Signaling in ROS Generation in Lung Cancer ROS-Dependent Gene Expression in Cancer Cells Anti-oxidative Stress (AOS) Genes HDAC Inhibition and ROS HDAC Inhibitor and YB1 Relation in ROS Production HDAC Inhibitors and ROS-Mediated Effects on Cancer Cells GBM vs. ROS HDAC Inhibitors in Bladder Cancer Resistance Against HDAC Inhibitors in Gastric Cancer HDAC Inhibitors in Rhabdomyosarcoma HDAC Inhibitors and Autophagy Systemic Approaches System Biology Approach on Regulation of Molecular Pathways by HDAC Inhibitors in Cancer Computational Approach in Drug Discovery Potential Application of HDAC Inhibitors in Inducing Apoptosis Conclusions and Future Directions References 163 Therapeutic Potential of Modulating Oxidative DNA Damage in Breast Cancer Introduction Role of Estrogens in Oxidative DNA Damage Oxidative Stress-Induced Chemoresistance in Breast Cancer Therapeutic Potential of Natural Products as Oxidative Stress Modulators Therapeutic Potential of Nanoparticles as Oxidative Stress Modulators Drug Repurposing References 164 Systems Biology and Bioinformatics Approaches Unraveling the Therapeutic Potential of Novel Drugs in Counteracting the Oxi... Bioinformatics Analysis of Differentially Expressed Genes Lipidomics Analysis Using Artificial Neural Networks Zinc Chelation Therapy Modulating Xenobiotic Metabolism Modulating NOTCH Signaling Targeting Arachidonic Acid Pathway Inducing Mitochondrial Stress Androgen Deprivation Therapy References Part VIII: Other Aspects of Therapeutics of ROS-Induced Cancer 165 Some Aspects of Oxidative Stress–Induced Prostate Cancer Therapy Introduction Prostate Cancer, Enzymatic Antioxidants, and Associated Biomolecules Prostate Cancer and Nonenzymatic Antioxidants Prostate Cancer and Noncoding RNA (ncRNAs) Prostate Cancer and MicroRNA Prostate Cancer and Inflammatory Oxidative Stress Oxidative Stress and DNA Damage in Prostatic Hyperplasia Genetic Modulation in PCa Cells by ROS GST Superfamily and PCa AR Signaling, Hormone Deprivation, and CRPC Outgrowth Androgen Deprivation Therapy (ADT) and CRPC Progression Interleukin-6 in Redox-Signaling Amplification in CRPC Cells Therapeutic Efficacy of Nrf2 Against CRPC Progression Role of NF-κB on AR Function Transcription Factors-Induced AR Expression and CRPC Development Conclusion and Future Perspectives References 166 Reactive Oxygen Species in Glioma Introduction Basic Biology of Glioma Current Standard of Therapy Oxidative Stress in Brain and CNS Oxidative Stress and Tumor-Associated Inflammations Oxidative Stress and Immune Cell Functionality ROS and Energy Homeostasis in Cancer Oxidative Stress and Circadian Rhythms Oxidative Stress and Therapy Resistance Conclusion and Future Direction References 167 Genetic Factors Contributing ROS-Driven Chemotherapy and Drug Resistance in Cancer Introduction Types of Chemotherapeutic Drugs The Role of ROS in Tumor Development ROS Plays Critical Role in Chemotherapeutic Drug Resistance Most Anticancer Drugs Use ROS to Kill Cancer Cells Through Common Molecular Pathways Identification of Genetic Factors Involved in Chemotherapeutic Drug Resistance Whole Genome Approach Identifying Genes for Chemotherapy Using Microarray Polymorphic Variants in ROS Modulatory Genes Play a Critical Role in Chemotherapy Role of DPYD Gene in Chemotherapy Implications References 168 Metabolic Oxidative Stress Introduction Metabolic Pathways in Cancer Metabolic Reprogramming: A Major Hallmark of Cancer Glucose Glutamine Lipid Scavenging and Fatty Acid Oxidation NADPH Relationship Between High Metabolic Rate and ROS Generation p53 and ROS Metabolism FOXOs and ROS Role of ROS in Cancer Progression Role in Angiogenesis ROS in Metastasis Metabolic Therapy: Evolving Role of Mitochondria in Metabolism Ketogenic Metabolic Therapy (KMT) Conclusions References 169 A CRISPR-Cas9-Based Therapeutics in Oxidative Stress-Induced Cancer Introduction ROS-Induced Carcinogenesis ROS-Induced Genetic Instability ROS-Induced Alteration of Signaling Pathways CRISPR-Cas9 in Cancer Research Application of CRISPR-Cas9 in Cancer Diagnosis Application of CRISPR-Cas9 in Cancer Therapeutics Application of CRISPR-Cas9 in the Generation of Cancer Models Role of CRISPR-Cas9 in Epigenetic Modifications in Oxidative Stress-Induced Cancer Limitations of the CRISPR-Cas9 in Cancer Therapeutics Concluding Remarks References 170 Molecular Mechanism of Oxidative Stress in Cancer and Its Therapeutics Introduction Production of ROS and Status of Endogenous Antioxidant in Tumorigenesis Association Between Oxidative Stress and Carcinogenesis Signaling Pathways Involved in ROS-Mediated Tumorigenesis ROS- and NF-kB-Mediated Tumorigenesis ROS- and MAPK/ERK -Mediated Tumorigenesis ROS- and Akt/PI3K/mTOR-Mediated Tumorigenesis ROS- and Tumor-Suppressive Genes ROS and Angiogenesis ROS and Tumor Initiation and Proliferation ROS and Tumor Survival and Invasion ROS and miRNA ROS, Mitochondrial Dysfunction, and Tumorigenesis Antioxidant and Prooxidant: Dichotomous Approach Toward ROS in Tumorigenesis Conclusion References 171 Pro-apoptotic Effects of Dietary Flavonoids in Oxidative Stress-Induced Cancer Introduction Oxidative Stress and Reactive Oxygen Species Regulation of ROS at Enzymatic Level Regulation of ROS at Molecular Levels Apoptosis: Pathways and Proteins Involved Intrinsic or Mitochondria-Dependent Pathway Extrinsic or Death Receptor-Induced Pathway Dietary Flavonoids with Pro-apoptotic Effect Against Experimental Cancers Quercetin Morin Epigallocatechin-3-Gallate Genistein Daidzein Apigenin Luteolin Myricetin Hesperidin Conclusion References 172 Redox Signaling Introduction Tumor Microenvironment (TME) Redox Microenvironment in Cancer Cell (RME) Redox Signaling and Cancer Cell Cycle Redox Signaling and Metabolic Rewiring in TME Redox-Mediated Cancer Progression Redox Signaling and Chemoresistance in Cancer Mechanisms of Chemoresistance (Table 5) Oxidative Stress-Mediated Activation of Autophagy ROS in ER Stress-Mediated Autophagy ROS and Cell Cycle Arrest Involvement of Epithelial-Mesenchymal Transition (EMT) and Cancer Stem-like Cells (CSC) in Chemoresistance Redox Balance and Chemoresistance Conclusion References 173 Mechanistic and Therapeutic Crosstalk of Lipid Peroxidation in Oxidative Stress and Breast Cancer Introduction Metabolic Adaptation of Breast Cancer Cell Epigenetics Glycolytic Shift Lipid Peroxidation and Underlying Mechanism Oxidative Stress in Angiogenesis and Apoptosis Inflammation Angiogenesis Redox Homeostasis Apoptosis Free Radicals and Antioxidant Dual Component ROS, RNS, and RCS Hereditary Crosstalk of Hypoxia Tumor Microenvironment Role of TAMs PHD2 and HIF1-α Targeted Therapy Conclusion and Future Perspective Challenges in the Area References 174 Therapeutic Implication of Oxidative Stress Regulators in Drug-Resistant Cancers Introduction Therapeutic Implication of Oxidative Stress Regulators in Drug-Resistant Cancers Mitochondrial Respiratory Chain Complex Regulators NOX Regulators GSH Regulators γ-GCS Regulators GPx Regulators GST Regulators SLC7A11 Regulators TrxR Regulators SOD Regulators HO-1 Regulators Nrf2- Keap1 Regulators UCP2 Regulators Prxs Regulators Other Key Proteins in Regulating Redox Homeostasis Other Small-Molecule Oxidative Stress Regulators Conclusion and Future Perspectives References 175 Y-Box-Binding Protein-1 Introduction YB-1 Structure and RNA/DNA Interactions Role of YB-1 in Oxidative Stress and Cancer Therapy YB-1 and Cancer YB-1 and Different Signaling Axis YB-1 and Ras-Extracellular Signal-Regulated Kinase/Mitogen-Activated Protein Kinase Signaling Inhibition of YB-1 and AKT Signaling YB-1 and HER2 Axis YB-1-Based Virotherapy for Cancer Treatment YB-1 and Immunotherapy for Cancer Treatment Conclusion References 176 Microbe-Induced Oxidative Stress in Cancer Development and Efficacy of Probiotics as Therapeutics in Preventing Its Onset ... Introduction Bacteria-Induced Oxidative Stress Promotes Cancer Development Oxidative Stress in the Digestive System Oral Carcinogenesis Oxidative Stress in the Gastrointestinal Tract Oxidative Stress in the Colon Oxidative Stress in the Reproductive System Oxidative Stress in the Respiratory System Bacterial Toxins Induced Cancer Development DNA-Damaging Toxins Colibactin Cytolethal Distending Toxin Cell-Signaling-Disrupting Toxins Cytotoxin-Associated Gene A (CagA) and Vacuolating Cytotoxin A (VacA) Cytotoxic Necrotizing Factor 1 Bacteroides fragilis Toxin Staphylococcal Enterotoxins Avirulence Protein A FadA The Role of Protozoa in Cancer Development Toxoplasma gondii Cryptosporidium parvum Trichomonas vaginalis Plasmodium falciparum and Burkitt Lymphoma Entamoeba histolytica Blastocystis hominis Giardia lamblia Therapeutic Roles of Probiotics in Cancer Treatment and Prevention Production of Antimicrobial Substances Improvement of Intestinal Barrier Modulation of the Immune System Antioxidant Properties of Probiotics Antiproliferative Activity of Probiotics Future Perspective References 177 Role of Forkhead Box Proteins in Regulating Epithelial-Mesenchymal Transition in Breast Cancer Introduction Breast Cancer: The Unconquered Human Malady Breast Cancer Types and Diagnosis Pathology of Breast Cancer and Staging Estrogen Signaling in Breast Cancer ER Stress-Manifested X-Box Protein 1-Binding Protein in Cancer The Discovery, Functions, and Significance of X-Box-Binding Protein in Breast Carcinogenesis Role of FOXO Transcription Factor as Regulators of Epithelial-Mesenchymal Transition Forkhead Box M1 and Malignancy: The Notorious Nexus Normal Physiological Roles and Functions of FOXO Family Cancer-Preventive Effects of FOXO Role of FOXO Proteins and X-Box-Binding Proteins on Oxidative Stress FOXO Proteins, X-Box-Binding Proteins and Apoptosis miRNA-Mediated Control of FOXO Expression in Cancer FOXOs and Autophagy The PI3K/Akt Signaling and FOXO Connection FOXO and Angiogenesis in Cancer FOXO and XBP1 as Targets in Breast Cancer Therapy Future Prospective Conclusion References 178 Targeting Mitochondria as a Novel Disease-Modifying Therapeutic Strategy in Cancer Introduction The Chemistry and Biology of ROS ROS: A Family of Reactive Oxygen Molecules Role of ROS in Cancer Progression Consequences of Oxidative Stress in Cancer ROS as an Initiator of Cancer ROS and Tumor Microenvironment Role of Oxidative Stress in Cancer Stem Cells ROS, Mitochondrial Fission/Fusion, and Cancer Therapeutic Potential of Oxidative Stress Pathways Inhibitors of Electron Transport Chain Induces ROS Production in Tumor Cells Inhibition of Antioxidant Enzyme System by Natural Products Mitochondrial Fission and Fusion for Therapy Combining Oxidative Stress Enhancers with Immunotherapy Conclusion and Future Direction References 179 Pathogenesis of Oxidative Stress in Lung Cancer and Its Therapeutic Aspects Introduction Pathogenesis of Lung Cancer Domestic Exposure Occupational Exposure Infections Environmental Smoke Smoking Tobacco Substances Causing Oxidative Stress Cigarette Smoking and Oxidants Oxidants and Silica (SiO2) Induced Particle Oxidants Asbestos and Oxidants The Role of Oxidants in Domestic Cooking Pathophysiology of Oxidants Oxidative Stress and Inflammation Oxidative Stress Induces DNA Alteration and Lung Cancer Degeneration of Lipid and Protein Imbalance of Oxidant/Antioxidant Role of Antioxidants in Lung Cancer Chemoprevention Antioxidant and Treatment of Lung Cancer Conclusion References 180 Modulators of ROS/NF-κB Signaling in Cancer Therapy Introduction NF-κB Signaling Pathway ROS/NF-κB Signaling Modulators f ROS/NF-κB Signaling Phenols Alkaloids Terpenoids Steroids and Saponins Polyketides Conclusions References 181 Targeting Tumors Through Enhancers of Oxidative Stress Introduction Etiology of Cancer Tobacco Environmental Carcinogens Diet, Obesity, and Physical Activity Mitochondrion Structural Components and Functions Structure of Mitochondria Mitochondrial DNA Functions of Mitochondria Electron Transport Chain in Mitochondria Reactive Oxygen Species in Mitochondria Mitochondrial Dysfunction Therapeutic Targets in Cancer Pathology Mitochondrial Medicine in Cancer Bioenergetic Therapy in Cancer Conclusion and Future Perspective References 182 Proteomics and Metabolomics in Cancer Diagnosis and Therapy Introduction Cancer Proteomics Proteomic Workflow Proteomics Platforms MS-Based Proteomic Approaches in Cancer Electrospray Ionization (ESI) and Matrix-Assisted Laser Desorption/Ionization (MALDI) SELDI-TOF QUEST-MS SPR-MS Chromatography Coupled with MS Non-MS-Based Proteomic Approaches in Cancer Biology Antibody-Based Platform Immunosensors Based on Lateral Flow Assay (LFA) Tissue Micro Array (TMA) Enzyme-linked Immunosorbent Assay (ELISA) Antibody Array Reverse-Phase Protein Array (RPPA) Single-Cell Proteomics in Cancer Cancer Metabolomics Metabolomics Workflow Metabolomics Analytical Platforms NMR MS GC-MS LC-MS Supercritical Fluid Chromatography (SFC) Capillary Electrophoresis (CE) Ion Mobility Spectrometry (IMS) DI-MS MALDI-MS Direct Analysis in Real-Time (DART)-MS Mass Spectrometry Imaging (MSI) Challenges and Opportunities Conclusions References 183 Oxidative Stress-Induced Autophagy Introduction Autophagy Machinery The Core Pathway of Mammalian Autophagy Molecular Mechanism of Autophagy Initiation Nucleation Elongation Maturation/ Fusion with Lysosomes Autophagy as an Adaptive Metabolic Response Intracellular Quality Control by Nonselective and Selective Autophagy Autophagy in Health and Disease CNS Diabetes Autophagy and Inflammation Crohn´s Disease Kidney Cardiovascular Diseases ROS and Autophagy Autophagy and Tumorigenesis Conclusion References 184 Antioxidant Supplementation Introduction (Length Depends on the Topic Describing Importance of Subject and Content) Main Text Antioxidant Supplementation: Paradoxical Role in Cancer Therapeutics Introduction Reactive Oxygen Species ROS Generation and its Regulations Role of ROS as Signaling Molecule Notch Pathway MAPK Pathway NFkB Pathway ROS-Driven Tumors Antioxidants Cancer Therapies and ROS Therapeutic Role of Antioxidant Supplementation in Cancer Pro-Tumorigenic Role of Antioxidants Conclusion References 185 Matrix Metalloproteinases (MMPs) in Cancer Immunotherapy Introduction MMPs and Tissue Inhibitors of Metalloproteinases (TIMPs) in Physiological Context Functional Roles of MMPs in Cancer Proteolysis of Extracellular Matrix Modulation of Cellular Interaction, Migration, and Metastasis Modulation of Growth Factors and Receptors Tumor-Associated Angiogenesis Regulation of Apoptosis Immunomodulation and Inflammatory Response Matrix Metalloproteinase Inhibitors (MMPIs) for Cancer Therapy Peptidomimetic MMPIs Non-peptidomimetic MMPIs Tetracycline Derivatives Off-Target MMPIs Other Novel Mechanism-Based Selective MMPIs Natural MMPIs Monoclonal Antibodies as MMP Inhibitors Matrix Metalloproteinase-Based Cancer Vaccines Strategies to Enhance Immune Response to MMP-Based DNA Cancer Vaccines Challenges and Future Prospect References 186 Pathogens and Cancer Introduction Pathogenic Infections, Oxidative Stress, and Cancer Helminth Parasites as Carcinogens Schistosomiasis haematobium Liver Flukes Cestodes Viruses as Carcinogens Human Papilloma Virus Hepatitis C Virus (HCV) Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Antioxidants as a Combinational Therapy for Cancer and Parasitic Infections Conclusions References 187 Susceptibility of Polymorphic GST as a Risk Factor in Oxidative Stress-Induced Cancer Development Introduction GST Genetic Variants GST in Cancers Role of GST in Lung Cancer Role of GST in Breast Cancer Role of GST in Liver Cancer Role of GST in Colorectal Cancer GST and Its Pharmacogenetics Conclusion and Future Prospectus References 188 Present Status of the Therapeutic Approaches to Treat Uveal Melanoma Introduction Genetic Contributors Therapeutic Options Chemotherapy Targeted Therapy Immunotherapy Checkpoint Inhibition Anti-CTLA-4 Therapy Anti-PD-1 Therapy Combined Inhibition of CTLA-4 and PD-1 Innovative Immune-Based Therapies Epigenetic Control Conclusions and Future Directions References 189 Reactive Oxygen Species–Induced Cancer Cell Death: A Therapeutic Approach Introduction Cancer Treatment Modalities Surgery Radiation Therapy Chemotherapy Immunotherapy Photodynamic Therapy Types of Reactive Oxygen Species (ROS) and Photochemical Reactions Sources of Reactive Oxygen Species Mitochondria Endoplasmic Reticulum Peroxisomes Exogenous Sources Cellular Responses to ROS-Induced Oxidative Stress ROS-Induced Apoptosis ROS-Induced Autophagy ROS-Induced Necrosis Conclusion and Future Perspectives References 190 Oxidative Stress in Cancer: Therapeutic Implications of Small-Molecule Kinase Inhibitors Introduction Small-Molecule Kinase Inhibitors (SMKIs) Protein Kinase Inhibitors Tyrosine Kinase Inhibitors (TKIs) Serine/Threonine Kinase Inhibitors PIM Kinase Inhibitors Lipid Kinase Inhibitors Dual PI3K/mTOR Inhibitors Pan-PI3K Inhibitors Isoform-Specific PI3K Inhibitors Conclusion Cross-References References 191 Novel Developmental Therapeutics Targeting Human Oral Squamous Cell Carcinoma Through Reactive Oxygen Species-Mediated Apo... Introduction Endoplasmic Reticulum Stress Has_circRNA_101036 as a Tumor Suppressor Activation of ROS-Dependent ER Stress Through Disulfiram (Antabuse) Alkylphosphocholine Erufosine as a Akt-mTOR Inhibitor Extracellular Signal-Regulated Kinase (ERK)/MAPK Pathway Isorhamnetin Dihydroartemisinin ROS-Regulated Mitochondrial Pathway Surfactin from Bacillus subtilis Lycorine Hydrochloride Plant-Based Extracts Azoxystrobin Arglabin Dietary Phytochemicals Current Trends and Future Prospects References 192 The Link Between Circadian Rhythm and ROS-Induced Cancer Introduction Circadian Rhythm Physiological Basis of Circadian Rhythm and its Importance Genetic Control of Circadian Rhythm The Link between Circadian Clock and Cancer ROS and Oxidative Stress Oxidative Stress and Cancer Cancer Cell vs Oxidative Stress and the Circadian Clock Conclusion References 193 Targeting the Antioxidant Enzymes for the Treatment of Reactive Oxygen Species (ROS)-Induced Cancer Introduction Antioxidant Enzymes Alterations in the Antioxidant Enzymes During ROS-Induced Cancer Alterations in Antioxidant Enzymes During Viral Induced ROS Production Role of Antioxidant Enzymes in the Regulation of Epithelial-Mesenchymal Transition (EMT) Antioxidant Enzymes as the Therapy/Therapeutic Target for Cancer Statin-Based Therapy SOD Mimics GPx Mimics CAT Mimics DNA-Damaging Drugs Conclusion References 194 A General Overview on Causes, Risk Factors, Diagnosis, Treatment, and Role of Oxidative Stress Biomarkers in Colorectal Ca... Introduction Etiology Molecular Pathophysiology of Colorectal Cancer Molecular Signaling Pathways Involved in Colorectal Cancer Wnt-β-Catenin Pathway PI3K-AKT Pathway RAS-RAF Pathway NF-κB Pathway GSK-3β (Acting as a Regulator in CRC Pathways) Epithelial-to-Mesenchymal Transition (EMT) Risk Factors Diagnosis Colonoscopy Capsule Endoscopy CT Colonography Magnetic Resonance Imaging (MRI) and Endorectal Ultrasound (ERUS) Biomarkers Treatment Approaches Surgery Colon Surgery Rectal Surgery Quality Assurance and Recovery Systemic Therapies for Primary CRC Neoadjuvant Therapy Adjuvant Therapy Systemic Therapies for Metastatic CRC Chemotherapy Targeted Therapies Role of Oxidative Stress Biomarkers in Colorectal Cancer Future Perspectives References 195 Oxidative Stress in the Pathogenesis of Ovarian Cancer Introduction Classification of OC Epithelial Cell Carcinoma (ECC) Germ Cell Cancer of the Ovary (GCC) Stromal Cell Cancer of the Ovary (SCC) Theories of Origin of OC (Saed et al. 2017) Oxidative Stress on Ovarian Cancer Common Ovarian Cancer Mutations Linked to ROS Drug Resistant OC and Nrf2 Gene (Li et al. 2021) Antioxidants and Therapeutic Targets in Ovarian Cancer (Amano et al. 2021) Conclusion and Future Perspectives References 196 Adipose-Derived Stem Cells Introduction ADSCs Characteristics Relationship Between ADSCs and Cancer Cells ``Tumor Niche´´ ADSCs Relationship with Reactive Oxygen Species ADSCs in Cancer Therapy Conclusions and Perspectives Cross-References References 197 Translational Reprogramming of mRNA in Oxidative Stress and Cancer Introduction An Outline of mRNA Translation mRNA Translation Initiation Translation Elongation and Termination Regulation of mRNA Translation Under Stress Integrated Stress Response Involves Rewiring of mRNA Translation mTOR Signaling Mediates Stress Adaptation by Controlling mRNA Translation Translational Repression Induces Stress Granule Formation tRNA Metabolism, Modification, and Cleavage Under Stress Impact mRNA Translation Oxidative Stress and Translational Reprogramming Oxidative Stress Induces Specific mRNA Translation Programs tRNA Metabolism Is Altered in Oxidative Stress Oxidative Stress Responsive Factors Modulate mRNA Translation Controlling mRNA Translation: A Remedial Avenue in Cancer Therapeutics Conclusions References 198 Regulation of Cellular Stress in the Light of mRNA Alternative Polyadenylation Introduction Cellular Stress Response Involvement of Cellular Processes in Stress Signaling Pathways Regulating Stress-mediated Cell Death Apoptosis Autophagy Necrosis Regulation of Cellular Responses to Cope With Stress ER Stress and Unfolded Protein Response DNA Damage Responses and Cell Death Oxidative Stress and Cell Death mRNA 3′ End Processing and Its Mechanism Cleavage/Polyadenylation Proteins Mechanism of Alternative Polyadenylation Regulation of Cellular Stress by Alternative Polyadenylation Role of Cleavage/Polyadenylation Factors in Stress Response Core Factors of APA Auxiliary Factors of APA The Role of Alternative Polyadenylation During DNA Damage Response Role of Alternative Polyadenylation in Oxidative Stress Role of Alternative Polyadenylation of Heat Shock Protein Encoding mRNAs Role of Alternative Polyadenylation for Stress Related to Nutrient Deficiency Role of Distal Polyadenylation Sites in Mammalian Cells in Response to Stress Conclusion Future Perspectives References 199 Impact of Chemotherapeutic Drugs Towards Oxidative Stress and Associated Multi-organ Physiological Responses Introduction Cardiotoxicity Chemotherapy-induced Cardiotoxicity Type I Chemotherapy-induced Cardiotoxicity Type II Hepatotoxicity 5-Flurouracil (5-FU) Methotrexate Irinotecan Oxaliplatin Tyrosine Kinase Inhibitors (TKIs) Tamoxifen Nephrotoxicity Cisplatin Ifosfamide Vascular Endothelial Growth Factor (VEGF) Inhibitors (Bevacizumab) Epidermal Growth Factor Receptor Inhibitors (Cetuximab) Peripheral Neuropathy Paclitaxel Oxaliplatin Thalidomide Conclusion and Future Perspectives References 200 The Role of Endothelin Axis and Reactive Oxygen Species in Future Therapies of Pancreatic Cancer Endothelin NADPH Oxidase and ROS Endothelin and Pancreatic Cancer Endothelin and Pancreatic Fibrosis Endothelin and Pancreatic Stellate Cell Activation Endothelin and Other Pancreatic Cells Endothelin and Pancreatic Microcirculation ROS and Pancreatic Cancer ROS and Pancreatic Fibrosis Hypoxia and Pancreatic Cancer ROS and Pancreatic Cancer Signaling DUOX1/2 and Pancreatic Cancer Conclusions and Future Therapy References 201 Targeting the Transcription Factors of ROS Tumorigenic Pathways as a Therapeutic Strategy in Cancer Introduction Transcription Factors in Cancer DNA Damage Response and p53 P53 Signaling Networks P53 Family Members P73 and Tumor Suppression P63 Signaling in Tumorigenesis Targeting p53 Signaling for Cancer Therapy Nuclear Factor-erythroid 2 p45-Related Factor-2 (NRF2) NRF2: A Master Hub for Regulating Cellular Homeostasis NRF2: A Pro-oncogene or Tumor Suppressor NRF2 as a Target for Cancer Therapy NRF2 Activation as a Therapeutic Strategy NRF2 Inhibition as a Therapeutic Strategy Hypoxia-Inducible Factors (HIFs) Conclusion References 202 Oxidative Stress in the Pathogenesis of Cervical Cancer Introduction Oxidative Stress and Cervical Cancer Human Papillomavirus (HPV) Genetic Alterations Diagnosis Treatment Conclusion and Future Perspectives References 203 Antioxidants in Oxidative Stress and Biocatalysts: Their Correlation with Cancer Introduction Oxidative Stress and Its Effect on the Body Oxidative Stress Also Contributes to Aging The Relationship Between Oxidative Stress and Cardiovascular Diseases Clinical Significance Enzymes and Antioxidants in Oxidative Stress The Antioxidants Reported Antioxidants in Medicinal Plants Discussion References 204 Biofluid Markers Unveiling Cancer Diagnosis and Prognosis: With Special Reference to Oxidative Stress Introduction Oxidative Stress as Biomarkers Biomarkers in Various Human Biospecimens Urinary Oxidative Stress Biomarkers Oxidative Stress-Related Salivary Biomarkers DNA Biomarkers RNA Biomarkers: Salivary MicroRNA Protein Biomarkers Lysozyme Alpha Amylase Isoprostanes Secretory IgA Oxidative Stress Biomarkers in Blood Blood MicroRNAs Heat Shock Proteins Enzymatic Antioxidants Nonenzymatic Antioxidants Cerebrospinal Fluid Biomarkers Related to Oxidative Stress Oxidative Stress Levels in Pleural Effusion Oxidative Stress Markers in Exhaled Breath Condensate Expression of Oxidative Stress Biomarkers in Tears Expression of Oxidative Stress Biomarkers in Sweat Trace Elements Dyshomeostasis in Cancer Biofluids Therapeutic Outcomes References Index