Cancer Research: An Interdisciplinary Approach

Preface
Contents
About the Editor
Interdisciplinary Approaches in Cancer Research
1 Introduction
2 What Is Interdisciplinarity?
3 Interdisciplinary Approach in Identifying Cancer Etiopathogenesis
4 Interdisciplinary Approach in Cancer Diagnosis
5 Interdisciplinary Approach in Cancer Treatment
6 Cancer Associated with Other Medical Conditions: Interdisciplinarity as the Solution?
7 Conclusion
References
Role of Immune Cells in the Tumor Microenvironment
1 Introduction
2 The Importance of T Cells in the TME
3 Role of Dendritic Cells in the Modulation of Antitumor T-Cell Responses
4 The Immune Landscape of Tumor-Infiltrating T and B Cells in Cancer
5 The Pivotal Role of T-Helper Cells in Tumor Immunity
5.1 T-Helper-2 Cells
5.2 T-Helper-17 Cells
References
Spatial Transcriptomic Approaches for Understanding the Tumor Microenvironment (TME)
1 Introduction
1.1 Cellular Components of TME
1.2 Noncellular Components of TME
1.3 Primary and Metastatic Site Comparison
2 Immunotherapy and Predictive Biomarkers
2.1 PD-L1
2.2 TMB
2.3 MSI
2.4 TLSs
2.5 IFN-γ
2.6 Microbiome
2.7 Adrenergic Neurons
2.8 Hypoxia
3 Spatial Phenotyping of the Tumor Microenvironment
3.1 Spatial Profiling Technologies for mRNA Expression
3.1.1 VIZGEN MERFISH
3.1.2 10x Genomics Visium
3.1.3 NanoString Technologies CosMx Spatial Molecular Imager
3.1.4 Resolve Bioscience Molecular Cartography
3.1.5 FISSEQ ReadCoor
3.2 Spatial Profiling Technologies for Protein Expression
3.2.1 Fluidigm Imaging Mass Cytometry (IMC)
3.2.2 Ionpath MIBI Technology
3.2.3 Akoya Biosciences CODEX
3.2.4 NanoString GeoMxTM DSP
4 Conclusion
References
Role of Mesenchymal Stem/Stromal Cells in Cancer Development
1 Introduction
2 Mesenchymal Stem/Stromal Cells
3 Immunoregulatory Properties of MSCs
4 Immunoregulator Mechanisms Observed in MSCs Derived from Tumors
5 Participation of EV-MSCs in Cancer Development
6 Other Mechanisms Used by MSCs to Stimulate Tumor Development
7 Conclusion
References
Cancer-Associated Fibroblasts and Their Role in Cancer Progression
1 Introduction
2 Fibroblasts and Their Origin with Specificity to CAFs
2.1 Normal Fibroblasts and Their Origin
2.2 Origin of CAFs: Effect of Factors Produced by Cancer Cells
2.3 Cancer Cells as Precursors of CAFs
3 Markers of CAFs
4 CAFs Influence the Biological Properties of Cancer Cells
4.1 CAFs Are Heterogeneous
4.2 CAFs Produce Growth Factors and Inflammation-Supporting Factors
4.3 CAFs Influence Immune Cells in the Cancer Ecosystem
4.4 CAFs Stimulate the Vascularisation of Tumours
4.5 The Systemic Effect of CAFs and Their Products on the Whole-Organism Scale
5 Tumour Evolution and Spreading at a Single Patient Level
6 CAFs in Diagnostics and Anti-cancer Therapy
6.1 Targeting Cytokine Signalling Pathways
6.2 Employment of Mesenchymal Stem Cells as Active Carriers with Suicidal Cargo
7 Conclusion
References
The Role of Tumoroids in Cancer Research
1 Introduction
2 Tumoroid Generation
3 Tumoroid Establishment
3.1 TME Components: Cellular Heterogeneity
3.2 TME Components: Extracellular Matrix (ECM)
4 Tumoroid Culture
4.1 Cell Sources
4.2 Conditioning Media
4.3 Culture Techniques
5 Tumoroid in Cancer Research
5.1 Tumoroid in Biological Research
5.1.1 Tumoroid in Molecular Biology of Cancer
5.1.2 Tumoroid in Cellular Biology of Cancer
5.2 Tumoroid in Biomedical Research
5.2.1 Tumoroid Biobanks
5.2.2 Tumoroid in Therapeutics
5.2.3 Tumoroid and Big Data
6 Conclusion
References
Myokine Expression in Cancer Cachexia
1 Introduction
Key Points
2 Muscle Wasting in Cancer Cachexia
3 Most Studied Myokines Involved in Cancer Muscle Cachexia
4 The Role of the Most Studied Myokines in Cancer
5 The Benefit of Physical Exercise in Cancer Cachexia
6 Conclusion
References
Epigenetics in Cancer Biology
1 Introduction
2 Types of Epigenetic Changes
3 DNA Methylation
4 Histone Posttranslational Modifications/the Incorporation of Histone Variants
5 RNA Interference
6 RNA Methylation
7 The Epigenetic Switch
8 Epigenetics Versus Genetics in Cancer
9 Epigenetic Biomarkers
10 Targeting Epigenetic Changes as Part of Cancer Therapy
11 Conclusion
References
Epigenetic Regulation of Cancer by Natural Touch: Phytochemicals and Epigenetic Regulation
1 Introduction
2 Phytochemicals and MicroRNAs
3 Phytochemicals and lncRNAs
4 Phytochemicals and Histone Modifications
5 Phytochemicals and DNA Methylation
6 Conclusions
References
Telomerase Reverse Transcriptase in Humans: From Biology to Cancer Immunity
1 Introduction
2 Telomerase in Human Cells
3 Role of Telomerase in Oncogenesis and Cancer Progression
3.1 Basic Cancer Cell Attributes Regulated by Telomerase
3.2 TERT and the Cellular Response to Stress in Cancer Cells
4 Regulation of TERT in Cancer Cells
4.1 TERT Gene Amplification
4.2 TERT Promoter Regulation
4.3 Post-transcriptional Regulation of TERT
5 Diagnostic and Prognostic Value of TERT
6 TERT as Immune Target
6.1 TERT-Specific T Cell Immunity
6.2 TERT-Based Immunotherapy
6.3 Immunity Against TERT and Immune Checkpoint Inhibitors
6.4 The TERT-MHC Relationship at the Population Level
7 Conclusion and Perspectives
References
Molecular Mechanisms of Metal-Induced Carcinogenesis
1 Introduction
2 The Role of Oxidative Stress in Metal-Induced Carcinogenesis
3 DNA Damage
3.1 Chromosomal Instability (CIN) and Formation of Micronuclei
3.2 Microsatellite Instability (MIN)
3.3 DNA Base Damage
3.4 Cross-Linking
3.5 Strand Scission
3.6 Abasic Sites
4 DNA Repair
4.1 Nucleotide Excision Repair (NER)
4.2 Base Excision Repair
4.3 Mismatch Repair
4.4 Direct Repair
4.5 Double-Strand Break Repair
5 Signal Transduction
5.1 Growth Factor Receptors
5.2 Ras
5.3 Src
5.4 MAPKs
5.5 NFκB
5.6 Nrf2
5.7 AP-1
5.8 NFAT
5.9 HIF-1
5.10 p53
6 Cell Cycle and Gene Expression
7 Epigenetic Modifications
7.1 DNA Methylation
7.2 Histone Modification
7.3 miRNA
8 Conclusion
References
Epi-Drugs Targeting RNA Dynamics in Cancer
1 Introduction
1.1 Transcription and RNA Processing
1.2 Transcription in Eukaryotic
1.3 Transcriptional Processing of RNA
1.4 Splicing
1.5 Alternative Splicing
2 Principal Types of RNA
3 Transcription and Epigenetic Regulation
3.1 Transcriptional Chromatin Epigenetic Modification
3.1.1 DNA Modifications
3.1.2 Histone Modifications
3.2 Transcriptional Epi-RNA Modifications
3.2.1 RNA Modifications
4 Noncoding RNA and Epitranscriptomic Deregulation in Cancer
5 Pharmaco-Epi-Transcriptomics in Cancer
5.1 RNA-Epidrugs Used in Cancer
5.2 Noncoding RNA Can Modulate Epigenetic Architecture in Cancer
6 Conclusion
References
Oncologic Emergencies: Pathophysiology, Diagnosis, and Initial Management
1 Introduction
2 Initial Management of the Acutely Ill Patient
2.1 Overview
2.2 Airway
2.3 Breathing
2.4 Circulation
2.5 Disability
2.6 Exposure
3 Oncologic Emergencies
3.1 Metabolic Oncologic Emergencies
3.1.1 Hypercalcaemia
3.1.2 Hyponatraemia
3.1.3 Tumour Lysis Syndrome
3.2 Haematologic Oncologic Emergencies
3.2.1 Disseminated Intravascular Coagulation
3.2.2 Neutropenic Fever
3.3 Cardiovascular Oncologic Emergencies
3.3.1 Malignant Pericardial Effusion and Cardiac Tamponade
3.3.2 Superior Vena Cava Syndrome
3.3.3 Venous Thromboembolism
3.4 Neurologic Oncologic Emergencies
3.4.1 Increased Intracranial Pressure
3.4.2 Malignant Spinal Cord Compression
3.5 Treatment-Related Oncologic Emergencies
3.5.1 Immune-Related Adverse Events Caused by Immune Checkpoint Inhibitors
4 Conclusion
References
Malignancies in Inborn Errors of Immunity
1 Introduction
2 Insights to the Pathogenesis of Malignancies in IEIs
3 Immunodeficiencies Affecting Cellular and Humoral Immunity
3.1 Severe Combined Immunodeficiencies (SCIDs)
3.2 Combined Immunodeficiencies with Less Profound T-Cell Defects
4 Combined Immunodeficiencies with Associated or Syndromic Features
4.1 Combined Immunodeficiencies Associated with Congenital Thrombocytopenia
4.2 Combined Immunodeficiencies Associated with DNA Repair Defects (Other than Listed Above)
4.3 Thymic Defects with Additional Congenital Abnormalities
4.4 Immune-Osseous Dysplasias
4.5 Hyper-IgE Syndromes
4.6 Calcium Channel Defects
4.7 Other Defects
5 Predominantly Antibody Deficiencies
5.1 Severe Reduction in All Serum Immunoglobulin Isotypes with Profoundly Decreased or Absent B-Cells, Agammaglobulinemia
5.2 Severe Reduction in at Least 2 Serum Immunoglobulin Isotypes with Normal or Low Number of B-Cells, CVID Phenotype
5.3 Isotype, Light Chain, or Functional Deficiencies with Generally Normal Numbers of B-Cells
6 Diseases of Immune Dysregulation
6.1 Familial Hemophagocytic Lymphohistiocytosis (FHL Syndromes)
6.2 FHL Syndromes with Hypopigmentation
6.3 Regulatory T-Cell Defects
6.4 Autoimmunity with or Without Lymphoproliferation
6.5 Immune Dysregulation with Colitis
6.6 Autoimmune Lymphoproliferative Syndrome (ALPS, Canale-Smith Syndrome)
6.7 Susceptibility to EBV and Lymphoproliferative Conditions
7 Congenital Defects of Phagocyte Number and Function
7.1 Congenital Neutropenias
7.2 Defects of Motility
7.3 Other Non-lymphoid Defects
8 Defects in Intrinsic or Innate Immunity
8.1 Mendelian Susceptibility to Mycobacterial Disease (MSMD)
8.2 Epidermodysplasia Verruciformis (HPV)
9 Autoinflammatory Disorders
10 Bone Marrow Failure
11 Phenocopies of Inborn Errors of Immunity
11.1 Associated with Somatic Mutations
11.2 Associated with Autoantibodies
12 Conclusion
References
Hematopoietic Stem Cell Transplantation in Patients with Inborn Errors of Immunity and Malignancy
1 Introduction
2 Hematopoietic Stem Cell Transplantation for Inborn Errors of Immunity
2.1 Improved Supportive Care
2.2 Accurate HLA-Typing and Donor Selection
2.3 Chemotherapy Conditioning
2.4 Graft Versus Host Disease
2.5 Endothelial Cell Activation Disorders
2.6 Disease-Specific Outcomes
2.6.1 Severe Combined Immunodeficiency
2.6.2 Chronic Granulomatous Disease
2.6.3 Wiskott-Aldrich Syndrome
2.6.4 CD40 Ligand Deficiency
2.6.5 DOCK8 Deficiency
2.6.6 DNA Double-Strand Break Repair Disorders
3 Hematopoietic Stem Cell Transplantation for Inborn Errors of Immunity and Malignancy
4 Secondary Malignancy Post-hematopoietic Stem Cell Transplantation
5 Conclusion
References
Personalized Immuno-Oncology with Immunodeficiency Mouse Models
1 Introduction
2 Cancer Treatment Goes from a Non-specific Approach to Personalized Therapy
2.1 Conventional Cancer Therapies Treat Cancers in a Non-specific Way
2.2 Cancer-Targeted Therapies Meet Their Waterloo
2.3 Immunotherapy Is a Significant Leap Forward in Cancer Treatment
3 Personalized Immuno-Oncology Therapies Are Probably the Answer for Cancer Heterogeneity
3.1 Cancer Is Unique in Each Patient
3.2 A Wide Variety of Personalized Cancer Immunotherapies Show Promising Results
3.2.1 Personalized Immune Checkpoint Inhibitors (ICI) Therapy
3.2.2 Cell-Based Personalized I/O Therapy
3.2.3 Personalized Cancer Vaccine
3.2.4 Novel Personalized Therapeutic Regimens
4 Patient-Derived Tumor Xenografts Preserve the Tumor Primitives
4.1 Conventional Tumor Models with Immunocompetent Mice
4.2 Immunodeficient Mouse Strains Support the Development of Xenogeneic Tumor Models
4.2.1 Athymic Nude Mice
4.2.2 Immunodeficient Mice
4.2.3 Severe Immunodeficiency Mice
4.2.4 Need for More Predictive Preclinical Efficacy Models
4.3 Patient-Derived Xenograft Models Make Co-clinical Trials Possible
4.3.1 Patient-Derived Xenograft Models
4.3.2 Characteristics of PDX Models and Their Applications in I/O Research and Therapy
4.3.3 Challenges of PDX Models
5 Humanized Mice with a Functional Human Immune System Are Ideal for I/O Treatment Evaluation
5.1 Development of Human Immune System (HIS) Mice in Immunodeficient Mice
5.2 PBMC-HIS Mice Are Easy to Establish and Are Suitable for Short-Term I/O Drug Testing
5.3 HSC-HIS Mice Contain a More Functional Human Immune Ystem and Are Suitable for Long-Term I/O Drug Testing
6 PDX-HIS Mice Reproduce Better Human Immune-Tumor Interactions
6.1 Allogenic PDX-HIS Mice Contribute to Personalized I/O Drug Development
6.2 Autologous PDX-HIS Mice Are Ideal Avatar for Co-clinical Trials
7 Conclusion
References
Allergy and Cancer: New Perspectives
1 Introduction
2 Related Immunological Components in Allergy and Cancer
2.1 IgE
2.2 Mast Cells
2.3 Histamine
2.4 Macrophages
2.5 Dendritic Cells
2.6 Innate Lymphoid Cells
2.7 Interleukin 12
2.8 IgG4 Antibodies
3 Current Data on Specific Cancers in Relation to Allergy
3.1 Hematological Malignancies
3.1.1 Acute Leukemia
3.1.2 Chronic Leukemia
3.1.3 Hodgkin Lymphoma and Non-Hodgkin Lymphoma
3.2 Breast Cancer
3.3 GI Cancers
3.3.1 Colorectal Cancer
3.3.2 Esophageal and Gastric Cancer
3.4 Skin Cancer
3.4.1 Squamous Cell Carcinoma and Early-Onset Basal Cell Carcinoma
3.4.2 Melanoma and Non-melanoma Skin Cancers
3.5 Cervical Cancer
3.6 Lung Cancer
3.7 Pancreatic Cancer
3.8 Brain Malignant Tumors
3.9 Prostate Cancer
3.10 Bladder Cancer
3.11 Head and Neck Cancer
4 Conclusion
References
Depression and Cancer: The Inflammatory Bridge
1 Introduction
1.1 Cancer and Inflammation
1.2 Depression and Inflammation
2 Dopamine and Immunity: Implications for Depression and Cancer Link
2.1 Dopamine and Depression
2.1.1 Repurposing Dopaminergic Drugs for Depression Treatment
2.2 Dopamine and Tumorigenesis
2.3 Dopamine and Inflammation
3 Conclusion and Perspectives
References
Impact of Cancer-Related Sarcopenia on Systemic Immune Status
1 Introduction
2 Sarcopenia in Cancer Patients
2.1 Relevance of Sarcopenia in Oncology
2.2 Immunological Status in Sarcopenic Cancer Patients
2.3 How Sarcopenia-Derived Immune Microenvironment Impacts on Cancer Progression
2.3.1 Myokines
2.3.2 Cross Talk Between Skeletal Muscle and Immune Cells
2.3.3 Prognostic Impact of Sarcopenia on Immunotherapy
3 Managing Sarcopenia in Clinical Practice
3.1 Operational Definition of Sarcopenia
3.2 Measurement of Variables
3.2.1 Skeletal Muscle Strength
3.2.2 Skeletal Muscle Quantity and Quality
3.2.3 Physical Performance
3.3 Cut-off Points for Measured Variables and Practical Algorithm
3.4 Development of Comprehensive Management Plan
4 Future Challenges
5 Conclusions
References
Surveillance of Subclinical Cardiovascular Complications in Childhood Cancer Survivors: Exercise as a Diagnostic and Therapeut...
1 Introduction
2 Treatment-Related Long-Term Complications in CCS
3 Early Detection and Intervention for Subclinical Cardiovascular Complications
4 Exercise as a Diagnostic and Therapeutic Modality to Prevent Long-Term Cardiovascular Complications in CCS
5 Education for Lifestyle Changes and Prevention Against Future Cardiovascular Disease
6 Conclusions
References
Index