Colon Cancer Diagnosis and Therapy Vol. 3

Preface
Contents
About the Editors
Updates on Clinical Trials in Diagnosis and Therapy of Colorectal Cancer
	1 Introduction
	2 Pathophysiology
	3 Screening and Diagnosis
	4 Management
		4.1 Agarose Tumor Macrobeads
		4.2 Anti-inflammatory Drugs
		4.3 Probiotics
		4.4 Functional Foods
		4.5 Metal-Based Drugs
			4.5.1 Platinum
			4.5.2 Gold-Based Drugs
	5 Conclusion and Future Perspectives
	References
Wnt Signaling-Related Long Noncoding RNAs: Critical Mediators of Drug Resistance in Colon Cancer
	1 Introduction
	2 Colon Cancer and Wnt Signaling
	3 Long Noncoding RNA in Colon Cancer
	4 Wnt Pathway-Related lncRNAs and Colon Cancer Metastasis
	5 Wnt Pathway-Related lncRNAs in Drug Resistance
	6 Wnt Pathway-Related LncRNAs in Colon Cancer Treatment
	7 Conclusion
	References
The Triad of Estrogen, Estrogen Receptors, and Colon Cancer
	1 Introduction
		1.1 Risk Factors for Colon Cancer
		1.2 Diet as a Major Risk Factor for CRC
		1.3 Etiology and Molecular Mechanisms Involved in the Development of CRC
		1.4 Treatment Strategies
	2 Estrogens: The Multifunctional Hormones
		2.1 Synthesis of Estrogens
		2.2 The Nuclear Receptor Superfamily
		2.3 Estrogen Receptors
		2.4 Nuclear Estrogen Receptors: Structure and Isoforms
		2.5 Membrane-Associated Estrogen Receptors
		2.6 G-Protein Coupled Estrogen Receptor 1 (GPER-1)
		2.7 Distribution of Estrogen Receptors
	3 Estrogen Signaling Pathways
		3.1 ER-Dependent, Nuclear-Initiated Estrogen Signaling (Genomic Effects)
		3.2 ER-Dependent, Membrane-Initiated Estrogen Signaling
		3.3 ER-Independent Signaling
		3.4 Ligand-Independent Activation of ERs
	4 Ligands
		4.1 Selective Estrogen Receptor Modulators (SERMS)
	5 Estrogen and Colon Cancer
		5.1 Location of Estrogen Receptors in the Colon
		5.2 Estrogen Function in Colonic Epithelium
		5.3 Estrogen Signaling Through Nuclear Receptors (α and β) in Colorectal Cancer
		5.4 Estrogen Signaling Through GPER in Colon Cancer
	6 Estrogen and Estrogen Receptors in the Prognosis of Colon Cancers
	7 Mechanisms of Antitumor Effects by Estrogen and Estrogen Receptors in Colon
	8 Hormone Replacement Therapy as a Potential Anticancer Strategy
	9 Conclusion
	10 Future Perspectives
	References
Clinical Significance of Genetic Variants in Colon Cancer
	1 Introduction
	2 Selected Potentially Clinically Significant SNPs in Colon Cancer
		2.1 APC Gene Mutation in Colon Cancer
		2.2 ATM Gene SNPs in Colon Cancer
		2.3 BRAF Gene Mutation and Colon Cancer
		2.4 BRCA1/BRCA2 Gene in Colon Cancer
		2.5 DUSP1 Gene SNPs in Colon Cancer
		2.6 MLH1 Gene in Colon Cancer
		2.7 MTHFR Gene SNPs in Colon Cancer
		2.8 MAP2K1 Gene SNPs in Colon Cancer
		2.9 SULT2B1 Gene SNPs in Colon Cancer
		2.10 VDR Gene SNPs in Colon Cancer
		2.11 MiRNA SNPs in Colon Cancer
	3 Conclusions
	References
Role of Nano-immunotherapy in Colorectal Cancer: An Updated Review
	1 Introduction
	2 Mechanism of Colorectal Cancer
	3 Immunology of Colorectal Cancer
	4 Role of Nanotechnology in Immunotherapy of CRC
	5 Conclusions
	References
Mechanistic Exploration and Therapeutic Management of Colon Cancer Metastasis
	1 Introduction
	2 Current Treatment of Colon Cancer
		2.1 Choice of First-Line Treatment
			2.1.1 Chemotherapy
			2.1.2 Therapeutics and Regimens
			2.1.3 Targeted Therapy
			2.1.4 Systemic Therapy for Advanced or Metastatic Disease (NCCN GUIDELINES)
		2.2 Sequence and Timing of Therapies
		2.3 Maintenance Therapy
			2.3.1 Bevacizumab
			2.3.2 Cetuximab and Panitumumab
	3 The Role of Primary Tumor Sidedness
	4 The Role of KRAS and NRAS Status
	5 HER2 Overexpression
	6 Cetuximab with FOLFIRI
	7 Panitumumab with FOLFIRI
	8 Cetuximab with FOLFOX
	9 Panitumumab with FOLFOX
	10 Therapy After Progression
		10.1 Cetuximab and Panitumumab in the Non-First-Line Setting
		10.2 Bevacizumab in the Non-First-Line Setting
		10.3 Ziv-Aflibercept
		10.4 Regorafenib
		10.5 Ramucirumab
		10.6 Trifluridine/Tipiracil (TAS-102)
		10.7 Pembrolizumab and Nivolumab
		10.8 Cetuximab or Panitumumab Versus Bevacizumab in Second-Line Setting
	11 Intestinal Flora
	12 Traditional Medicine
	13 Other Therapies
	References
Chemoresistance in Colorectal Malignancies: Molecular Mechanisms and Strategies to Overcome.
	1 Introduction
	2 Chemoresistance in CRC
	3 Immunotherapy
	4 Chemoresistance Pathways Associated with Colorectal Cancer
	5 Tumor Microenvironment
	6 Epithelial/Mesenchymal Transition
	7 Autophagy
	8 Therapeutic Potential for CRC
	9 Conclusion
	References
Therapeutic Intervention of Signaling Pathways in Colorectal Cancer
	1 Introduction
	2 Alteration in Signaling Pathway Gene
	3 Molecular Targeted Therapy in Treatment of Cancer
		3.1 The EGFR and EGFR-Associated Pathways
		3.2 Targeting EGFR, RAS/RAF/MEK/ERK Signaling
		3.3 Role of HGF/c-MET Pathway in CRC
		3.4 The Vascular Endothelial Growth Factor (VEGF)/Vascular Endothelial Growth Factor Receptor (VEGFR) Pathway as a Therapeutic Target for Colorectal Cancer
		3.5 Notch Signaling Pathway as a Therapeutic Target for Colorectal Cancers
		3.6 PI3K Signaling Pathway as a Therapeutic Target for Colorectal Cancers
		3.7 TGF-β Signaling Pathway as a Therapeutic Target for Colorectal Cancers
		3.8 Wnt Signaling Pathway as a Therapeutic Target for Colorectal Cancers
		3.9 Src Family Kinases (SFKs) in Colorectal Cancer
		3.10 The Hedgehog (Hh) Signaling Pathway in Colorectal Cancer
		3.11 Immune Escape and Cancer Immunotherapy
	4 Cytotoxic Chemotherapeutic Drugs for the Treatment of Colorectal Cancer
	5 Targeted Chemotherapeutic Drugs for the Treatment of Colorectal Cancer
		5.1 FDA-Approved Targeted Drugs
			5.1.1 Monoclonal Antibodies (mAb)
				Bevacizumab
				Ramucirumab
				Cetuximab
				Panitumumab
				Nivolumab and Ipilimumab
				Pembrolizumab
			5.1.2 Small-Molecule Therapy in Colorectal Cancer
				Regorafenib
				Ziv-Aflibercept
		5.2 Other Targeted Drugs of Potential Therapeutic Value
			5.2.1 Napabucasin
			5.2.2 Nintedanib
			5.2.3 Vatalanib
			5.2.4 Semaxanib
			5.2.5 Cediranib
			5.2.6 Brivanib
			5.2.7 Apatinib
	6 Conclusion
	References
Targeting Pathogenic Inflammation for Therapeutic Intervention Against Colon Cancer
	1 Introduction
	2 Epidemiology
		2.1 Incidence
		2.2 Mortality
	3 Pathophysiology
	4 Molecular Factors Influencing CRC
		4.1 Genomic Instability
		4.2 Vascular Endothelial Growth Factor (VEGF)
		4.3 Ras Family
		4.4 p53
		4.5 BRAF V600E
	5 Cancer Cellular Immunotherapy
		5.1 T-Cell and Cancer Immunotherapy
			5.1.1 CAR T-Cell Therapy
			5.1.2 Natural Killer (NK) Cell Therapy
			5.1.3 Tumor-Infiltrating Lymphocyte (TIL) Therapy
		5.2 Myeloid Cells and Cancer Immunotherapy
			5.2.1 Tumor-Associated Macrophages (TAMs) and Cancer Immunotherapy
			5.2.2 Neutrophils and Cancer Immunotherapy
	6 Limitations for Cellular Immunotherapy
	7 Conclusion
	8 Research Questions
	References
Role of Tumour-Associated Macrophages in Colon Cancer Progression and Its Therapeutic Targeting
	1 Introduction
	2 Distinctive Status of TAM
	3 TAM and Colorectal Tumorigenesis
		3.1 Role in Tumour Progression
		3.2 Role in Tumour Microenvironment and Tumour-Induced Immunosuppression
		3.3 Role in Angiogenesis
		3.4 Role in ECM Remodelling
		3.5 Role in Metastasis
		3.6 Role in Chemoresistance
	4 Therapeutic Targeting of TAM
		4.1 Limiting the Number of Macrophage in TME
		4.2 TAM Reprogramming for Antitumour Immune Response
	5 Conclusion
	References
Advances in Chemoradiotherapy for Treatment of Colon Cancer
	1 Introduction
	2 Chemotherapy for CRC
	3 Radiation Therapy of CRC
	4 Chemoradiotherapy for CRC
	5 Approaches to Improve the Therapeutic Index of Chemoradiotherapy
	6 Radiosensitizer and Mode of Action
	7 Mechanisms of Drug-Radiation Interactions
	8 Chemoradiation for CRC
	9 Conclusion
	References
Cytotoxic and Chemopreventive Activity of Polyphenols and Their Derivatives in Colon Cancer
	1 Introduction
		1.1 Polyphenols
			1.1.1 Polyphenol Compounds: Sources and Their Dietary Intake
		1.2 Chemical Properties
		1.3 Classification
	2 Cancer
		2.1 Colon Cancer
	3 Polyphenols’ Role in Colon Cancer
	4 Polyphenols with Anticolon Cancer Activity
		4.1 EGCG-Epigallocatechin 3-Gallate
		4.2 Chlorogenic Acid
		4.3 Curcumin
		4.4 Caffeic Acid
		4.5 Apigenin
		4.6 Genistein
		4.7 Quercetin
		4.8 Resveratrol
		4.9 Ellagic Acid
		4.10 Flavone (2-Phenyl-4H-1-Benzopyran-4-One)
		4.11 Carsonic Acid
		4.12 Gingerol
		4.13 Silibinin
		4.14 Luteolin
		4.15 Tangeretin
	5 Mechanisms of Anticancer Activity By Polyphenols
		5.1 Anti-Inflammatory Effect
		5.2 Pro-Oxidation and Anti-Oxidation
		5.3 Pro-Apoptotic Effect
		5.4 Effects on the Signaling Pathway/Signaling Route
			5.4.1 In the MAPK Pathway
			5.4.2 PI3K/Akt Signalling
			5.4.3 The Wnt/β-Catenin Pathway
			5.4.4 The 67 kDa Laminin Receptor Pathway
			5.4.5 The NF-κB Pathway
			5.4.6 The JAK/STAT Pathway
			5.4.7 The Nrf2-Related Factor Pathway
		5.5 Modulation of Gut Microbiota
		5.6 Epigenetic Mechanism
			5.6.1 DNA Methylation
			5.6.2 miRNA
		5.7 Other Factors
			5.7.1 Anti-Angiogenesis
			5.7.2 Effect on Phase I and II Enzymes
			5.7.3 Cell Cycle Arrest
			5.7.4 Inhibition of Metastasis
	6 Conclusion
	References
Prevention and Management of Colon Cancer by Nutritional Intervention
	1 Introduction
	2 Fruits
		2.1 Punica granatum (Pomegranate)
		2.2 Citrus
		2.3 Malus domestica (Apple)
		2.4 Berries
		2.5 Vitis vinifera (Grapes)
		2.6 Banana
	3 Vegetables
		3.1 Cruciferous Vegetables
		3.2 Allium Vegetables
		3.3 Other Vegetables
	4 Whole Grains
		4.1 Wheat Bran
		4.2 Rice Bran
		4.3 Oatmeal
	5 Spices
		5.1 Curcuma longa (Turmeric)
		5.2 Zingiber officinale (Ginger)
		5.3 Nigella sativa (Black Cumin)
	6 Milk Product
		6.1 Calcium
		6.2 Vitamin D3
		6.3 Butyric Acid and Conjugated Linoleic Acid
	7 Conclusion
	References
Role of Food Additives and Intestinal Microflora in Colorectal Cancer
	1 Introduction
	2 Food Additives
	3 Risk Associated with Food Additives
	4 International Numbering System (E Numbers) of Food Additives
	5 Categories of Food Additives and Associated Risk
		5.1 Food Preservatives
			5.1.1 Antimicrobial Agents
				Nitrates and Nitrites
			5.1.2 Antioxidants
			5.1.3 Antibrowning Agents
		5.2 Food Coloring Agents
		5.3 Flavoring Agents
		5.4 Texturizing Agents
		5.5 Nutritional Additives
	6 Role of Intestinal Microflora in Colorectal Cancer
	7 Conclusion
	References
Effect of Milk and Dairy Products in Colorectal Cancer
	1 Introduction
	2 Milk Constituents
	3 Milk Products and Colorectal Cancer
	4 Fermented Dairy Products, Probiotics, and Prebiotics
	5 Conclusion
	Bibliography
Development of RNA-Based Medicine for Colorectal Cancer: Current Scenario
	1 Introduction
	2 Colorectal Cancer Therapy Based on RNA
		2.1 Antisense Oligonucleotide (ASO)
		2.2 Ribozymes
		2.3 RNA Aptamer
		2.4 RNA Interference (RNAi)
			2.4.1 siRNA
			2.4.2 MicroRNA (miRNA)
			2.4.3 Long Non-coding RNAs (lncRNAs)
			2.4.4 Small Activating RNAs
	3 Improvement for Enhanced Ability of RNA Therapeutics for Colorectal Cancer
		3.1 Modification of RNA Chemical Structure
		3.2 Nanoparticles Mediate Targeted RNA Delivery to Colorectal Cancer Cells
	4 Pros and Cons in Developing RNA-Based Therapeutics
	5 Conclusion
	References
Bacterial Cancer Therapy: Promising Role in the Treatment of Colon Cancer
	1 Introduction
	2 Bacteria as Therapeutics in Cancer Treatment
	3 Probiotic Bacteria as a Tool in Cancer Prevention and Therapy
	4 Bacterial Toxins as Therapeutics in Cancer Immunotherapy
		4.1 Diphtheria Toxin
		4.2 Pseudomonas Exotoxin A (PE)
		4.3 α-Hemolysin of Staphylococcus aureus
		4.4 Anthrax Toxin
		4.5 Limitations of Immunotoxins for Their Successful Use in Cancer Therapy
	5 Bacteriocins as Therapeutic in Cancer Treatment
		5.1 Several of These Bacteriocins Are Effective Against Colon Cancer and Other Cancer Cell Lines
	6 Nonribosomal Bacterial Peptides as Therapeutic in Cancer
	7 Bacterial Enzymes as Therapeutic in Cancer Treatment
	8 Combination of Bacteriotherapy with Conventional Therapy
		8.1 Bacteriotherapy-Radiotherapy Combination
		8.2 Bacteriotherapy-Chemotherapy Combination
	9 Conclusion
	References
Antineoplastic Effects of Curcumin Against Colorectal Cancer: Application and Mechanisms
	1 Introduction
	2 Colon Cancer
		2.1 Initiation of Colorectal Cancer
		2.2 Treatment Strategy for Colorectal Cancer
			2.2.1 Stage 0 Colorectal Cancer and Its Treatment
			2.2.2 Stage I Colorectal Cancer and Its Treatment
			2.2.3 Stage II Colorectal Cancer and Its Treatment
			2.2.4 Treatment of Stage III Colorectal Cancer
			2.2.5 Treatment of Stage IV Colorectal Cancer
	3 Biological Activity of Curcumin
		3.1 Anticancer Activity
		3.2 Anti-inflammatory and Antioxidant Activities
		3.3 Immune-Regulatory Activity
		3.4 Cardiovascular Protection
		3.5 Antidiabetic Effects
		3.6 Neuroprotection
	4 Use of Curcumin Against Colon Cancer
	5 Use of Curcumin Analogues in Colon Cancer Prevention and Therapy
	6 Colon Cancer Prevention by Curcumin Through Epigenetic Modifications
	7 Curcumin Drug Delivery in Colon Cancer
	8 Curcumin as a Modulator of the Gut Microbial Environment
	9 Immunomodulatory Effects of Curcumin in Colon Cancer
	10 Conclusion
	References
Role of Chemokines in Colorectal Cancer
	1 Introduction
	2 Mechanisms of Colorectal Cancer
	3 Potential Causes Associated with CRC
	4 Chemokines and Chemokine Receptors
	5 Chemokine Receptors Work in Metastasis
	6 Chemokines and Their Receptor in Colorectal Cancer
	7 CC Family of Chemokines and Their Receptors CCR
		7.1 CCL2 and CCR2
		7.2 CCL5 and CCR5
		7.3 CCL15 and CCR1
		7.4 CCL19/21 and CCR7
		7.5 CCL20 and CCR6
		7.6 CCL24 and CCR3
	8 CXC Family of Chemokines and Their Receptors CXCR
		8.1 CXCL1/5/8 and CXCR2
		8.2 CXCL9/10 and CXCR3
		8.3 CXCL12 and CXCR4/CXCR7
	9 CX3C Family of Chemokines and Their Receptors CX3CR
		9.1 CX3CL1 and CX3CR1
	10 Chemokines and Their Receptors as Potential Biomarker in Cancer Immunotherapy
	References
Index