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

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