Drug Resistance in Colorectal Cancer: Molecular Mechanisms and Therapeutic Strategies (Volume 8) (Cancer Sensitizing Agents for Chemotherapy (Volume 8))

Description

Drug Resistance in Colorectal Cancer: Molecular Mechanisms and Therapeutic Strategies, Volume Eight, summarizes the molecular mechanisms of drug resistance in colorectal cancer, along with the most up-to-date therapeutic strategies available. The book discusses reasons why colorectal tumors become refractory during the progression of the disease, but also explains how drug resistance occurs during chemotherapy. In addition, users will find the current therapeutic strategies used by clinicians in their practice in treating colorectal cancer. The combination of conventional anticancer drugs with chemotherapy-sensitizing agents plays a pivotal role in improving the outcome of colorectal cancer patients, in particular those with drug-resistant cancer cells. From a clinical point-of-view, the content of this book provides clinicians with updated therapeutic strategies for a better choice of drugs for drug-resistant colorectal cancer patients. It will be a valuable source for cancer researchers, oncologists and several members of biomedical field who are dedicated to better treat patients with colorectal cancer. Cover Cancer Sensitizing Agents for Chemotherapy DRUG RESISTANCE IN COLORECTAL CANCER: MOLECULAR MECHANISMS AND THERAPEUTIC STRATEGIES Copyright Aims and Scope for Series ``Cancer Sensitizing Agents for Chemotherapy´´ About the Editors About the Series Editor Aims and Scope of the Volume Preface References Contributors 1 Drug resistance in colorectal cancer: General aspects Introduction Development of fluoropyrimidines Resistance mechanisms for fluoropyrimidines Activation and inactivation Inhibition of thymidylate synthase FU incorporation into RNA DNA directed effects of 5FU Downstream effects of 5FU Mechanism of action of TAS-102 and resistance Metabolism of trifluorothymidine Resistance to trifluorothymidine and TAS-102 Mechanism of action and resistance to topoisomerase inhibitors Mechanism of action Resistance mechanism of irinotecan Mechanisms of action and resistance to oxaliplatin Mechanism of action Cellular resistance mechanisms of platinum analogs Clinical resistance of oxaliplatin The role of pharmacogenetics/pharmacogenomics in resistance Conclusions Acknowledgments References 2 Drug transporters in the development of multidrug resistance in colorectal cancer Introduction Overview about colorectal cancer Treatment options for CRC ATP-binding cassette transporters and CRC ABC transporter family ABC transporters and CRC initiation ABC transporters and multidrug resistance to cancer chemotherapy Clinical evidence for the role of ABC transporters in MDR of CRC Overexpression of P-gp in colon cancer at diagnosis leads to intrinsic drug resistance ABCG2 overexpression drives self-renewal and chemoresistance of CD133-positive human CRC cells Expression of MRP1 in circulating tumor cells (CTC) Pregnane X receptor (PXR) overexpression and its transcriptional activation of multidrug resistance-related protein-3 (MRP- ... Circumvention of MDR in CRC by evasion of ABC transporters General approaches Recent resurgence in the interest of using MDR transporter inhibitor to overcome drug resistance Inhibition of MDR transporters by tyrosine kinase inhibitors Inhibition of MDR transporters by constituents derived from natural sources Other approaches to inhibit ABC transporters for MDR circumvention in CRC HIF-1α inhibition reverses MDR in CRC cells by downregulating P-gp miR-519c precursor and chemical HuR inhibitors suppress ABCG2 overexpression in CRC to overcome MDR Inhibition of the nucleoside P2 receptors to downregulate MRP2 expression and potentiate anticancer drugs in CRC Challenges and future prospective of important research developments that may potentially impact the field Conclusion Acknowledgments References 3 Role of colorectal cancer stem cells in resistance to apoptosis and treatment in colorectal cancer Introduction Colorectal cancer stem cells Activation of multiple signal transduction pathways in colorectal CSCs CSCs and progression of colorectal cancer Contribution of colorectal CSCs in resistance to cancer treatment Colorectal CSCs and cancer recurrence Therapy resistance mechanisms in CSCs Therapy resistance due to overexpression of multidrug transporters Musashi homolog 1 and drug resistance in colorectal CSCs Antiapoptotic proteins and drug resistance in CSCs MicroRNAs are important regulators of drug resistance in colorectal CSCs Conclusion Acknowledgments References 4 Serrated lesions and stem cells on drug resistance and colon cancer Introduction Stem cells in the serrated lesions of human colon CD133 LGR5 DCLK1 β-Catenin helix Olfactomedin 4 and claudin-18 Therapy of the serrated lesions Drug resistance in serrated lesions Conclusion Acknowledgment References 5 Development of novel microRNA-based therapeutics platform for colorectal cancer Introduction Biogenesis of miRNAs and their involvement in colorectal cancer (Table 1) miRNA, p53, and colorectal cancer Impact of miRNAs in cancer stem cells Combating colon cancer stem cells with miRNAs Modified miRNAs as therapeutics Summary and future perspectives Acknowledgments References 6 Chemo-sensitizing agents from natural origin for colorectal cancer: Pharmacodynamic and cellular pharmacokinet ... Introduction Autophagy and chemo-resistance Tumor hypoxia and chemo-resistance Nuclear factor-κB (NF-κB) and chemo-resistance TRAIL receptors (death receptors) and chemo-resistance Survivin and chemo-resistance The ubiquitin-proteasome system and chemo-resistance Pharmacokinetics chemo-resistance Compounds of natural origin and cancer Phenolics Terpenoids Miscellaneous compounds Compounds from marine and microbial origin Conclusion Acknowledgment References 7 Induction of programmed necrosis by phytochemicals in colorectal cancer Introduction Phytochemicals overcoming drug resistance via inducing programmed necrosis Phytochemicals inducing necroptosis in colorectal cancer Phytochemicals induce ferroptosis in colorectal cancer Phytochemicals induce other nonapoptotic programmed necrosis in colorectal cancer Conclusions and future perspectives Acknowledgments References 8 Predictive biomarkers of drug resistance in colorectal cancer-Recent updates Introduction Associated miRNAs in chemoresistant CRC Other noncoding RNAs as biomarkers for chemoresistant CRC Recent updates on protein biomarkers as predictors of chemoresistance in CRC Conclusion and future perspective Acknowledgments References 9 Rac1b: An emerging therapeutic target for chemoresistance in colorectal cancer Introduction NF-κB, cancer, and chemoresistance Rac1 and the oncogenic splice variant Rac1b Rac1b is overexpressed in colorectal adenocarcinoma Rac1b signaling in colorectal cancer Rac1b confers resistance to chemotherapy Pharmacologic targeting of Rac1b Conclusion Acknowledgments References 10 Nanotechnology-based targeted drug delivery systems and drug resistance in colorectal cancer Introduction Mechanisms of drug resistance in colorectal cancer Nanomedicines and cancer drug resistance Bypass drug efflux transporters with nanoparticle delivery systems Nano-based modulation of intracellular drug release pH-triggered drug release nanoparticles Enzyme-activated nanoparticles Redox-responsive drug release External stimulus-responsive nanoparticles Organelle-targeting drug delivery for overcoming drug resistance Nuclear-targeting delivery Mitochondria-targeting nanomedicines Codelivery systems for synergistically overcoming drug resistance Nanotechnology for remodeling TME to reverse MDR Degradation of the extracellular matrix Reprogramming tumor-associated macrophages Antiangiogenic therapy Nanomedicines for treating drug-resistant colorectal cancers Nanotechnology-based monotherapy Nanotechnology-based codelivery of chemotherapeutics and nucleic acid drugs Nanotechnology-based codelivery of small drugs Combination of cytotoxins and molecularly targeted agents Combination of cytotoxins and immunological checkpoint inhibitors Combination of cytotoxins and active ingredients isolated from traditional Chinese herbs Combination of cytotoxins and proteins Combination of therapeutic antibody and small interfering RNA Conclusions Acknowledgments References 11 Targeting colorectal cancer via nanodrug delivery systems Introduction Nanomedicines The history of nanomedicines The EPR effect Molecular pathogenesis of colorectal cancer Adenoma-carcinoma sequence Genetic mode DNA methylation Microsatellite instability POLE gene mutation Multiple signaling pathways Application of nanotechnology in the treatment of colorectal cancer Nanoliposomes Nano micelles Nanoscale microbubbles Carbon nanotubes Magnetic nanomaterials Mesoporous silica nanoparticles Application of nanotechnology in the detection of colorectal cancer Conclusion and prospect Acknowledgments References Index Back Cover