Gastrointestinal Cancers: An Interdisciplinary Approach: An Interdisciplinary Approach (Interdisciplinary Cancer Research, 4)

Preface
Contents
About the Editor
Interdisciplinary Approach in Gastrointestinal Cancers
	1 Introduction
	2 Primary Tumor Sites and Types of Gastrointestinal Cancers
	3 History of Gastrointestinal Cancers
	4 Epidemiology of Gastrointestinal Cancers
	5 Mortality and Morbidity of Gastrointestinal Cancers
	6 Interdisciplinary Approach in Gastrointestinal Cancers
		6.1 Interdisciplinary Approach in the Diagnosis of Gastrointestinal Cancers
		6.2 Interdisciplinary Approach in the Treatment of Gastrointestinal Cancers
			6.2.1 Approved Therapies
				Immune Checkpoint Blockade
				CD73 and Adenosine Receptor Subtype
				Cancer Vaccination
				Adoptive Cell Therapy
				Conversion of Cold Tumors to Hot Tumors
				Oncolytic Viruses
			6.2.2 Treatment Plans Based on Involved Organ
				Esophagus Cancer
				Gastric Cancer
				Liver Cancer
				Pancreatic Cancer
				Colorectal Cancer
				Gallbladder Cancer
			6.2.3 Therapies Under Development
	7 Conclusion
	References
Gastrointestinal Cancers: What Is the Real Board of Microenvironment and the Role of Microbiota-Immunity Axis?
	1 Introduction
	2 The Borders of GIT Microenvironment
	3 The New ``Actors´´ of the TME: The Gut Microbiota and Its Metabolites
		3.1 The Microbiota of the Gastrointestinal Tract
		3.2 Alteration of Microbiota in the GI Cancers
		3.3 Microbial Post-biotics of the GI Tract
	4 The Microbiota-Immunity Axis
		4.1 The ``Immune´´ TME
		4.2 The Role of Microbiota-Immunity Axis in Gastrointestinal Cancers
	5 Targeting TME for Cancer Immunotherapies
	6 Conclusion
	References
Epithelial-Mesenchymal Transition in Gastrointestinal Cancer: From a Basic to a Clinical Approach
	1 Introduction
	2 Epithelial Plasticity and EMT Subtyping in Cancer
	3 Molecular Pathways of EMT: General Data
	4 Esophageal Squamous Cell Carcinoma
	5 Gastric and Gastroesophageal Cancer
	6 Cancer of the Small Intestine
		6.1 Adenocarcinoma and Carcinoma of Ampulla of Vater
		6.2 Gastrointestinal Stromal Tumor (GIST)
	7 Colorectal Cancer
	8 Pancreatic Cancer
		8.1 Pancreatic Ductal Adenocarcinoma (PDAC)
		8.2 Neuroendocrine Tumors (NETs)
	9 Hepatobiliary Cancers
		9.1 Hepatocellular Carcinoma (HCC)
		9.2 Cholangiocarcinoma
	10 Future Challenges
		10.1 EMT and Migrastatic Drugs
		10.2 EMT and Targeting Immune Checkpoints
		10.3 EMT and Melatonin
		10.4 EMT and Dexamethasone
	11 Conclusion
	References
Metabolomics of Gastrointestinal Cancers
	1 Introduction
	2 Different Metabolic Approaches
		2.1 Mass Spectrometry
		2.2 Nuclear Magnetic Resonance Spectroscopy
		2.3 Other Approaches
	3 Metabolic Alterations in GI Cancers
		3.1 Metabolomics and Pancreatic Cancer
		3.2 Metabolomics and Colorectal Cancer
		3.3 Metabolomics and Liver Cancer
		3.4 Metabolomics and Gastric Cancer
		3.5 Metabolomics and Esophageal Cancer
	4 Conclusion
	References
Deregulation of Immune System in Gastric Cancer Development, How Immune Nutrition Might Restore the Functions of Immune Cells
	1 Introduction
		1.1 Epidemiology and Pathogenesis
		1.2 Histology
		1.3 Molecular Landscape
		1.4 Tumour Microenvironment
		1.5 Tumour Immune Escape
		1.6 Immunotherapy in Gastric Cancer
	2 Immune Nutrition
		2.1 Immune Nutrition in Gastric Cancer
		2.2 Effects of Immune Nutrition on Tumour Microenvironment
	3 Conclusion
	References
Helicobacter pylori Virulence Factors, Pathogenicity, and Gastric Cancer
	1 Introduction
		1.1 Adaptation in the Acidic Environment
			1.1.1 Urease Activity
			1.1.2 Flagella and Chemotaxis System
		1.2 Attachment to Host Cells (Adhesins)
		1.3 Pathogenicity of H. pylori
			1.3.1 Vacuolating Cytotoxin A
			1.3.2 Cytotoxin-Associated Gene A (CagA)
	2 Concluding Remarks
	References
Gastric Cancer and Helicobacter pylori
	1 Introduction
	2 Incidence, Prevalence, and Mortality of Gastric Cancer: Adenocarcinoma
	3 Histologic Classification
	4 H. pylori as a Carcinogen and Gastric Cancer Pathogenesis
	5 Routes of Transmission of H. pylori Infection
	6 Virulence Factors
	7 Can H. pylori Treatment Reduce the Risk of Gastric Cancer?
	8 Gastric Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma
	9 Conclusions
	References
Role of Neuromodulators in Regulation of the Tumor Microenvironment of Gastric and Colorectal Cancers
	1 Introduction
	2 Sources of the Neurotransmitters in GI Tract
	3 Role of Important Neuromodulators in Modulating the TME of Gastric and Colorectal Cancers
		3.1 Acetylcholine
		3.2 Catecholamines
			3.2.1 Epinephrine and Norepinephrine
			3.2.2 Dopamine
		3.3 Serotonin
		3.4 Nitric Oxide
		3.5 γ-Aminobutyric Acid
		3.6 Neuropeptides
			3.6.1 Neuropeptide Y
			3.6.2 Substance P (SP)
			3.6.3 Vasoactive Intestinal Peptide
	4 Conclusion
	References
The Role of Tumor Microenvironment in Colon Cancer
	1 Introduction
	2 TME and Colorectal Cancer
	3 Immune Cellular Compartment of TME
		3.1 Jass and Klintrup-Makinen Scores
		3.2 Crohn´s-Like Reaction
		3.3 TIL Evaluation on H&E
		3.4 Combined Assessment
		3.5 Immune Cell Subsets
		3.6 TAMs (Tumor-Associated Macrophages)
		3.7 TANs (Tumor-Associated Neutrophils)
	4 Stromal Cellular Compartment of TME
		4.1 Cancer-Associated Fibroblasts (CAFs)
	5 TME and Mismatch Repair System
	6 The Relationship Between TME and Chemotherapy in CRC
	7 TME and Metastatic CRC
	8 TME Validated Scores
		8.1 Tumor-Stroma Ratio
		8.2 Immunoscore
	9 TME Analysis and Digital Pathology
	10 TME as a Therapeutic Target
	11 Conclusion
	References
Unraveling the Esophageal Cancer Tumor Microenvironment: Insights and Novel Immunotherapeutic Strategies
	1 Introduction
	2 Immune System
	3 Immune System-Mediated Esophageal Cancer Initiation Progression
		3.1 Myeloid-Derived Suppressor Cells
		3.2 Regulatory T Cells
		3.3 T Helper 17 Cells
		3.4 Tumor-Associated Macrophages
		3.5 Cancer-Associated Fibroblasts
	4 Targeted Immunotherapy in EC
	5 Conclusion and Future Directions
	References
The Interplay Between Immunity and Gut Microbiota in Colon Cancer
	1 Introduction
	2 Gut Microbiota
		2.1 Microbiota-Associated Mechanisms of Carcinogenesis
	3 Clinical Value of the Microbiota
		3.1 Biomarkers for CRC Screening and Prognosis
		3.2 Microbiota Modulation for CRC Prevention and Treatment
		3.3 Gut Microbiota Interplay in Patients Undergoing Chemotherapy After CRC Surgery
		3.4 Effects of Gut Microbiota on Immunotherapy
	4 Conclusion
	References
Immunotherapy in Gastrointestinal Cancer Focusing on CAR-T Cell Therapy
	1 Introduction
	2 Immune System
		2.1 Tumor Microenvironment (TME) Role in Immunotherapy
		2.2 Cancer-Immunity Cycle
	3 Types of Immunotherapies in GI Cancers
		3.1 Immune Checkpoint Inhibitors (ICIs)
		3.2 Tumor Antigen Vaccine Therapies
		3.3 Adoptive Cell Therapy (ACT)
	4 CAR-T Cell Therapy
		4.1 Anti-tumor Mechanism of CAR-T Cell Therapy
		4.2 Targeted Antigens Expressed on GI Tumors
	5 Side Effects and Limitations of CAR-T Cell Therapy
		5.1 Side Effects
		5.2 Limitations
	6 How to Improve the Safety of CAR-T Cell Therapy?
		6.1 Immune Inhibitory Receptors
		6.2 On-Switch CAR
	7 Conclusion
	References
Development of Biocompatible Nanocarriers for the Treatment of Colorectal Cancer
	1 Introduction
		1.1 Colorectal Cancer and Its Management
		1.2 Limitations of Medication-Based Therapies Against CRC
	2 Development of Nanocarriers Against Cancer
		2.1 Properties of Nanocarriers
		2.2 Types of Nanocarriers
			2.2.1 Organic Nanoparticles
			2.2.2 Inorganic Nanoparticles
			2.2.3 Hybrid Nanoparticles
	3 Construction of Biocompatible Nanocarriers for Colorectal Cancer Treatment
		3.1 Biomaterials Used for Biocompatible Drug Nanocarrier Synthesis
		3.2 Potent Nanocarriers Against Colorectal Cancer
	4 Limitations and Future Perspectives
	5 Conclusion
	References
Challenges of Onco-therapeutics in Early-Onset Colorectal Cancer
	1 Introduction
	2 Total Neoadjuvant Therapy and the Potential for Nonoperative Treatment
	3 Challenges and Consequences of Pelvic Radiotherapy
	4 Implications of Chemotherapeutics in Early-Onset Colorectal Cancer
	5 The Growing Use of Cancer Immunotherapy
	6 Conclusion
	References
Unintentional Weight Loss and Malnutrition After Esophageal Cancer and Treatment
	1 Introduction
	2 Diagnosis and Staging
	3 Treatment and Management of Esophageal Cancer
	4 Survival
	5 Weight Loss and Nutritional Compromise in All Stages of Esophageal Cancer (EC)
	6 The Impact of Esophagectomy on Nutritional Status
	7 What Are the Consequences of Weight Loss and Malnutrition Associated with Esophagectomy?
		7.1 Negative Impact on Quality of Life
		7.2 Reduced Long-Term Survival due to Inability to Tolerate Adjuvant Treatments
	8 Pathophysiological Mechanisms of Weight Loss Following Esophagectomy
		8.1 Changes in Gut Hormones, Bile Acids, and Gut Microbiota After Esophagectomy Gut Hormone Changes After Esophagectomy
		8.2 Alterations in Bile Acid Signaling Following Esophagectomy
		8.3 Alterations to Gut Microbiota Following Esophagectomy
	9 Parallel Contributory Factors to Weight Loss Post-esophagectomy
		9.1 Surgical Technique
		9.2 Appetitive Behavior
		9.3 Systemic Inflammatory Response
		9.4 Cancer Cachexia
		9.5 Change in Dietary Intake
		9.6 Dumping Syndrome
		9.7 Psychological Factors
		9.8 Micronutrient Deficiencies
	10 Nutritional Support Following Esophagectomy
	11 Conclusion
	References
Current Clinical Landscape of Immunotherapeutic Approaches in Pancreatic Cancer Treatment
	1 Introduction
	2 Tumor Microenvironment in Pancreatic Cancer
		2.1 Macrophages and Myeloid-Derived Suppressor Cells (MDSCs)
			2.1.1 Role of Macrophages in TME
			2.1.2 Role of MDSCs in TME
		2.2 Natural Killer (NK) Cells
		2.3 Neutrophils
		2.4 T Lymphocytes
			2.4.1 T Helper (TH) Cells: TH1, TH2, and TH17
			2.4.2 Regulatory T Cells (Tregs)
			2.4.3 Cytotoxic T Lymphocytes (CTLs)
	3 Immunotherapeutic Approaches to Pancreatic Cancer
		3.1 Oncolytic Virus Therapy (OVT)
		3.2 Adoptive Cell Transfer Therapy
			3.2.1 Tumor-Infiltrating Lymphocyte (TIL) Therapy
			3.2.2 Genetically Modified T Cells
				TCR-Engineered T-Cell Therapy
				CAR T-Cell Therapy
				CAR-NK Cell Therapy
				Cytokine-Induced Killer (CIK) Cell Therapy
		3.3 Immune Checkpoint Blockade (ICB)
		3.4 Cancer Vaccines
		3.5 Immunotherapeutic Strategies Based on Targeting Myeloid Cells and CAFs
			3.5.1 Targeting Macrophages
			3.5.2 Targeting CAFs
			3.5.3 Reprogramming Dendritic Cells
			3.5.4 Targeting Immunosuppressive Myeloid Cells
	4 Conclusion
	References
The Tumor Microenvironment in Pancreatic Cancer and Challenges to Immunotherapy
	1 Introduction
		1.1 Immunotherapy
		1.2 Pancreatic Cancer
	2 Immune Signatures of Tumors
		2.1 Hot, Cold, Immunosuppressed and Excluded Tumors
	3 The Characteristics of the TME in PDAC
		3.1 Immune Cells
			3.1.1 Tumor-Infiltrating Lymphocytes
			3.1.2 Natural Killer Cells
			3.1.3 Myeloid-Derived Suppressor Cells (MDSCs)
			3.1.4 Tumor-Associated Macrophages (TAMs)
		3.2 Immune Checkpoints
			3.2.1 PD-1 and PD-L1
		3.3 Stroma and Fibrotic Tissue
			3.3.1 Cancer-Associated Fibroblasts (CAFs)
		3.4 Upregulated Signaling Pathways
			3.4.1 SMAD4 and TGF-β
		3.5 Driver Mutations
			3.5.1 KRAS
		3.6 Neoantigens and Hypermutability
			3.6.1 Tumor Mutational Burden
			3.6.2 Mismatch Repair Proteins
	4 Conclusion
	References
Index