Breaking Tolerance to Pancreatic Cancer Unresponsiveness to Chemotherapy: Volume 5

Description

Breaking Tolerance to Pancreatic Cancer Unresponsiveness to Chemotherapy, edited by Dr. Nagaraju focuses on overriding the resistance from chemotherapeutic drugs with a broader range of treatment options. It particularly focuses on stroma, tumor microenvironment, stem cells, stellate cells, transcription factors, growth factors, and important signaling pathways. This volume discusses topics such as pancreatic cancer biology, current therapeutic options, EMT, chemotherapy resistance mechanisms, and genetic manipulations and natural products to enhance the sensitivity of pancreatic cancer to chemotherapy. Additionally, it discusses small targeted molecules and pancreatic cancer trials, and nanotechnology-based drug delivery. Breaking Tolerance to Pancreatic Cancer Unresponsiveness to Chemotherapy is a valuable source for researchers and advanced students in cancer and oncology as well as clinicians and medical students who are interested in learning more about ways to break pancreatic cancer resistance to chemotherapy. Modulates the biologic properties of stroma in pancreatic cancer by targeting the several chemotherapy resistance mechanisms to impede their malignant property by introducing new strategies and drugsProvides information about on-going research as well as clinical data on pancreatic cancer and detailed descriptions about therapeutic options for easy understandingUtilizes full color figures to help the understanding of the content and tables for easy comparison of information as well as quick access to it Cover BREAKING TOLERANCE TO PANCREATIC CANCER UNRESPONSIVENESS TO CHEMOTHERAPY Copyright Dedication Contributors About the Editor About the Series Editor Aims and Scope for Series ``Cancer Sensitizing Agents for Chemotherapy´´ Preface 1 Overview of Pancreatic Cancer Biology Conflict of Interest Introduction Pathogenesis and Molecular Biology Three Biological Stages of Cancer Development Initiation Clonal Expansion Oncogenesis KRAS Raf/Mitogen-Activated Protein Kinase (MAPK) Cascade Phosphoinositide 3-Kinase/ATK Cascade Nuclear Factor Kappa B Signaling Cascade Tumor Suppressor Genes CDKN2A TP53 SMAD4 Introduction to Local and Distant Microenvironments Familial Pancreatic Cancers Conclusions References Further Reading 2 Chemoresistance in Pancreatic Cancer: Emphasis on Age and Gender Conflict of Interest Introduction Pancreatic Cancer Incidences and Prognosis: Association of Age and Gender Chemoresistance: Association With Age and Gender Mechanisms Associated With Chemoresistance Factors Modulated in Various Age Groups Conclusion Acknowledgments References 3 EMT Contributes to Chemoresistance in Pancreatic Cancer Conflict of Interest Introduction Pancreatic Cancer Metastasis EMT Regulation in Pancreatic Cancers ZEB1 SNAIL Twist PRRX1 (Paired Related Homeobox 1) Signaling Pathways Involved in the Regulation of EMT TGF-β Wnt/β-catenin Notch TNF-α EMT in Chemoresistance in Pancreatic Cancer 5-Flurouracil Chemoresistance Gemcitabine Chemoresistance Role of EMT in Gemcitabine Resistance Promising Ways to Improving Gemcitabine Efficacy Conclusions and Future Perspectives Acknowledgments References 4 Pancreatic Cancer Resistance to Gemcitabine Conflict of Interest Introduction Gemcitabine Structure and Mechanism Gemcitabine Sensitivity Gemcitabine and Chemoresistance Role of Gemcitabine in Targeting Signaling Pathways Conclusion Acknowledgment References 5 Pancreatic Cancer and Possible Therapeutic Options Conflict of Interest Introduction Reasons Behind the Above Statistics? Brief Outline of Treatment Tumor-Node-Metastasis Staging and Clinical Classification Modalities for Evaluating TNM Staging Clinical Classification Treatment Options for Pancreatic Adenocarcinoma Localized Surgically Resectable Stage I and II Disease Adjuvant Therapy Gemcitabine and 5-Fluorouracil Gemcitabine and S-1 Gemcitabine and Capecitabine Adjuvant Chemoradiation Gemcitabine Plus Nab-Paclitaxel Neoadjuvant Therapy Adjuvant Therapy in Borderline Removable Pancreatic Carcinoma Evidence Supporting Neoadjuvant Therapy FOLFIRINOX as Neoadjuvant Therapy NAC-GSL (Neoadjuvant Chemotherapy-Gemcitabine, S-1, LV) Metastatic Pancreatic Cancer: Treatment Options Early Period First-Line Therapies FOLFIRINOX PRODIGE-4/ACCORD-11 Trial Outcomes of PRODIGE-4/ACCORD-11 Trial Precautionary and Toxicity Reducing Strategies Gemcitabine Plus Nab-Paclitaxel The MPACT Trial When to Use FOLFIRINOX Versus Gemcitabine/Nab-paclitaxel? Clinical Parameters Indicating the Preferred Regimen Regimen Selection for Poor Performance Status Patients Second-Line Options 5-FU Plus Oxaliplatin-Based Combination Nanoliposomal Irinotecan and 5-FU/Leucovorin Combination The NAPOLI-1 Trial Newer Treatment for Pancreatic Carcinoma KRAS Inhibitors RAF/MEK/ERK HER-2 Inhibitors Epidermal Growth Factor Receptor Inhibitors JAK/STAT Inhibitors Insulin-Like Growth Factor 1 Receptor Inhibitor Vascular Endothelial Growth Factor Receptor Inhibitors Tumor Stroma/Desmoplasia Transforming Growth Factor-β Platelet-Derived Growth Factor Hyaluronic Acid Matrix Metalloproteinase Inhibitors Hedgehog Inhibitors Conjugated Drugs Nab-Paclitaxel PEP02 (MM-398) Endo Tag-1 Trastuzumab Emtansine Tumor Hypoxia Conclusions and Future Perspectives References 6 Curcumin and Genistein Enhance the Sensitivity of Pancreatic Cancer to Chemotherapy Conflict of Interest Introduction Chemotherapy for Pancreatic Cancer Tumor Microenvironment Developing Chemoresistance Curcumin Effecting as a chemo-sensitizer Genistein Effecting as a Chemo Sensitizer Signaling Cascades EGFR VEGF STAT Pathway Mitochondrial Pathway MiRNAs Notch Signaling Pathway Epigenome Changes Bioavailability Conclusion Acknowledgment References 7 Terpenoids as Potential Targeted Therapeutics of Pancreatic Cancer: Current Advances and Future Directions Conflict of Interest Introduction Pancreatic Cancer Risk Factor of Pancreatic Cancer Terpenoids Molecular Targets of Terpenoids in Pancreatic Cancer Terpenoids as NF-κB Signaling Inhibitors Terpenoids in the Regulation of Caspase Activity Terpenoids With Targeting DNA Damage Terpenoids Targeting Apoptotic Proteins Terpenoids With Differential Targets in Pancreatic Cancer Conclusion Acknowledgment References Further Reading 8 Small Molecules and Pancreatic Cancer Trials and Troubles Conflict of Interest Pancreatic Cancer: Causes and Treatments Causes and Prevention Therapeutic Treatments Pancreatic Cancer Resistance Causes of Treatment Resistance Combatting the Various Chemotherapy Resistance Pathways Pancreatic Cancer and Small Molecules General Overview of Small Molecules Heat Shock Proteins and HSP90 in Pancreatic Cancer HSP90 Inhibitors in Clinical Trials Acknowledgment References 9 Targeting the Epigenome as a Therapeutic Strategy for Pancreatic Tumors: DNA and Histone Modifying Enzymes Conflict of Interest Introduction DNA Methylation and Demethylation Histone Deacetylation and Acetylation Inactivating Histone Methylations Activating Histone Methylations Conclusions and Future Perspectives Acknowledgments References 10 Are Nanocarriers Effective for the Diagnosis and Treatment of Pancreatic Cancer? Conflict of Interest Current Status About Pancreatic Cancer Commonly Used Therapeutic Agents Chemotherapy Radiation Therapy Nanoscience and Nanotechnology Nanocarriers Polymeric Nanoparticle Polymeric Micelle Liposome Nanogel Mesoporous Inorganic Nanoparticle Metal Oxide Nanoparticle Inorganic Carbon Nanotubes Nanoparticles Used in Pancreatic Cancer References 11 Molecular Markers for Treatment Response and Toxicity of Gemcitabine Conflict of Interest Introduction Gemcitabine Transport and Metabolism of Action Dosing Toxicities with Gemitabine Candidate Genes Affecting Gemcitabine Therapy Neucleoside Transporter Genes SLC28 Family Gene Polymorphisms SLC29 Family Genes of Metabolizing Enzymes Cytidine Deaminase Deoxycytidine Kinase Deoxycytidylate Deaminase Cytidine Monophosphate Kinase 1 Thymidylate Synthase Genes of Drug Targets Ribonucleotide Reductases 1 Conclusions References Index A B C D E F G H I J K L M N O P R S T U V W X Z Back Cover