Cancer Stem Cells: Basic Concept and Therapeutic Implications

✍ Scribed by Farhadul Islam (editor), Alfred K. Lam (editor)

• Publisher: Springer
• Year: 2023
• Tongue: English
• Leaves: 375
• Edition: 1st ed. 2023
• Category: Library

✦ Synopsis

This book comprehensively reviews the role of cancer stem cells (CSCs) in cancer initiation, progression, and resistance to anticancer therapies. The initial chapters examine the methods and procedure of the detection, isolation, and characterization of CSCs. It also introduces various epigenetic pathways that contribute to cancer initiation and tumorigenesis, particularly regarding the maintenance and survival of CSCs. It also explores the role of CSCs metabolism and the mechanisms of metabolic plasticity of CSCs in cancer biology. Further, it also presents the implications of CSCs on the origin of tumor heterogeneity and on heterogeneity of the therapeutic response. Towards the end, this book highlights the different immunotherapeutic approaches targeting CSCs with the potential of strongly improving cancer outcomes. This book offers a broad framework to scientists and clinicians into the state-of-the-art knowledge on cancer stem cell biology and highlights their therapeutic implications.

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✦ Table of Contents

Foreword
Preface
Acknowledgment
Contents
Editors and Contributors
1: Introduction and Perspective in Carcinogenesis
1.1 Introduction
1.2 Cancer Stem Cells (CSCs): Origin and Roles in Carcinogenesis
1.3 Detection and Isolation of CSCs in Various Cancers
1.4 Clinical Significance of CSCs
1.5 Future Perspective: Therapeutics Targeting CSC
1.6 Conclusion
References
2: Origin and Development of Cancer Stem Cells
2.1 Introduction
2.2 Stem Cell Definition
2.3 Stem Cell Models
2.4 Cancer Two-Step Model
2.5 History of Cancer Stem Cells (CSCs)
2.5.1 Nineteenth Century
2.5.2 Twentieth Century
2.5.3 Twenty-First Century
2.5.4 Symmetric and Asymmetric Model of CSC Development
2.5.5 Genetic Mutations and Signaling Model of CSC Development
2.5.6 Microenvironment Model of CSC Development
2.5.7 Embryonic Model of CSC Development
2.6 Conclusions
References
3: Detection and Isolation of Cancer Stem Cells
3.1 Introduction
3.2 Detection and Isolation of Stem Cell
3.3 Expansion to CSCs: Cell Sorting Methods
3.4 The Leukemia Stem Cell: Initial Biomarkers
3.5 Transition to Solid Tumor CSCs: Biomarker Variability
3.6 Focus on CSC Quiescence: Side Population (SP) Analysis
3.7 Functional Isolation: In Vitro Tumorsphere, Tumorigenicity, and Chemoresistance Assays
3.8 Current State of Isolation and Detection Methods: Concluding Statements
References
4: The Genetic and Epigenetic Landscape of Cancer Stem Cells
4.1 Introduction
4.2 Genetics of Cancer Stem Cells
4.3 Epigenetics of Cancer Stem Cells
4.4 Histone Modification
4.5 DNA Methylation
4.6 Chromatin Remodeling
4.7 Noncoding RNAs
4.8 Genetic and Epigenetic Makeup of CSC and Inflammation
4.9 Clinical Significance of CSC Genetic and Epigenetic Changes
4.10 Concluding Remarks/Conclusion
References
5: Metabolism of Cancer Stem Cell
5.1 Introduction
5.2 The Metabolic Profile of Cancer Cells
5.3 The Metabolic Profile of CSCs
5.3.1 Primary Glycolytic CSCs
5.3.2 Oxidative Phosphorylation (OXPHOS)-Dependent CSCs
5.3.3 Glutamine Metabolism in CSCs
5.3.4 Lipid Metabolism in CSCs
5.4 Metabolic Complexity of CSCs
5.5 Roles of Mitochondria in CSC Phenotype
5.6 Therapeutics Targeting Metabolism of CSC
5.7 Concluding Remarks and Challenges Ahead
References
6: Plasticity of Cancer Stem Cell
6.1 Introduction
6.2 CSCs Capture the Developmental Program of Normal Stem Cell
6.3 Tumor Microenvironment and Plasticity of CSCs
6.4 Metabolic Adaptation in the Plasticity of CSCs
6.5 Epigenetic Regulation of Plasticity in CSCs
6.6 Therapy Resistance and CSC Plasticity
6.7 Conclusion
References
7: Cancer Stem Cells in Cancer Initiation and Progression
7.1 Introduction
7.2 Introduction to Cancer Stem Cells
7.3 Wnt/β-Catenin, Sonic Hedgehog, and Notch Signaling Pathways
7.4 CSC Hypothesis: Breast Cancer
7.5 CSC Plasticity and Targeting
7.6 Therapeutic Strategies
7.7 Conclusion
References
8: Cancer Stem Cells and Metastasis
8.1 Introduction
8.2 CSCs and the Primary Tumor Site Niche
8.3 CSCs and EMT
8.4 CSCs and the Pre-metastatic Niche
8.5 CSCs and the Metastatic Niche
8.6 Dormancy, MET, and Angiogenesis
8.7 CSCs and Origin of Metastasis
8.8 Molecular Markers of Cancer Metastasis
8.8.1 Colorectal Cancer
8.8.2 Breast Cancer
8.8.2.1 Glioblastoma
8.8.2.2 Lung Cancer
8.8.2.3 Pancreatic Cancer
8.9 Conclusion
References
9: Roles of Cancer Stem Cells in Therapy Resistance and Disease Recurrence
9.1 Introduction
9.2 The Role of CSC in Resistance to Hematologic Cancer Treatment
9.3 Breast Cancer
9.4 Ovarian Cancer
9.5 Lung Cancer
9.6 Prostate Cancer
9.7 Colorectal Cancer
9.8 Esophageal Cancer
9.9 Liver Cancer
9.10 Conclusion
References
10: Novel Therapeutics Targeting Cancer Stem Cell Surface Markers
10.1 Introduction
10.2 Cancer Stem Cell Surface Markers
10.2.1 Acute Myeloid Leukemia
10.2.2 Hepatocellular Carcinoma (HCC)
10.2.3 Gynecological Cancer
10.2.4 Non-small Cell Lung Cancer
10.2.5 Breast Cancer
10.2.6 Prostate Cancers
10.2.7 Brain Cancer
10.2.8 Bladder Cancer
10.2.9 CSC Surface Marker-Targeted Therapy for Other Malignancies
10.3 Conclusions
References
11: Therapeutics Targeting Cancer Stem Cell Signalling Pathways
11.1 Introduction
11.2 Overview of Signalling Pathways in Cancer Stem Cells
11.2.1 Wnt/β-Catenin Signalling Pathway
11.2.1.1 Wnt Signalling in CSCs
11.2.2 Notch Signalling Pathway
11.2.2.1 Notch Signalling in CSCs
11.2.3 Hedgehog Signalling Pathway
11.2.3.1 Hedgehog Signalling in CSCs
11.2.4 NF-Kβ Signalling Pathway in CSCs
11.2.4.1 Canonical NF-Kβ Signalling
11.2.4.2 Non-canonical NF-Kβ Signalling
11.2.4.3 NF-Kβ Signalling in CSCs
11.2.5 JAK-STAT Signalling Pathway
11.2.5.1 JAK-STAT Signalling in CSCs
11.2.6 TGF-β/Smad Signalling Pathway
11.2.6.1 TGF-β/Smad Signalling Pathway in CSCs
11.2.7 PI3K/Akt/mTOR Signalling Pathway
11.2.7.1 PI3K/Akt/mTOR Signalling Pathway in CSCs
11.3 Therapeutics Targeting Signalling Pathways in Cancer Stem Cells
11.3.1 Agents Targeting the Wnt/β-Catenin Pathway
11.3.2 Agents Targeting the Notch Pathway
11.3.3 Agents Targeting the Sonic Hh Pathway
11.3.4 Agents Targeting the NF-kB Pathway
11.3.5 Agents Targeting JAK-STAT Pathway
11.3.6 Agents Targeting TGF-β Pathway
11.3.7 Agents Targeting the PI3K Pathway
11.4 Conclusion
References
12: Cancer Stem Cell Therapeutic Delivery and EPR Effect
12.1 Introduction
12.2 Enhanced Permeability and Retention (EPR) Effect
12.3 Factors of EPR Effect-Based Drug Delivery
12.3.1 Availability of Vascular Mediators
12.3.2 Degree of Vascular Density
12.3.3 Stromal Content
12.3.4 Blood Coagulation
12.3.5 Blood Flow Dynamics
12.3.6 Blood Viscosity
12.3.7 Reticuloendothelial System (RES)
12.3.8 Physicochemical Properties of Nanomedicine
12.3.9 Intra-tumor Release Rate of API
12.4 Strategies to Enhance EPR
12.4.1 Blood Pressure Manipulation
12.4.2 Vascular Mediator Supplementation
12.4.2.1 Bradykinin (BK)
12.4.2.2 NO-Generating Agents
12.4.2.3 CO-Generating Agents
12.4.2.4 Prostaglandins (PGs)
12.4.2.5 Cytokines
12.4.3 Anti-thrombosis Agents
12.4.4 Physical Interventions
12.4.5 Photo-immunotherapy
12.4.6 RES Uptake Suppression
12.4.7 Intra-tumor Distribution of API
12.4.7.1 pH-Triggered Cleavage of API for Releasing Free Dugs
12.4.7.2 Protease-Mediated Cleavage
12.4.7.3 External Stimuli-Mediated Cleavage
12.4.8 Intracellular Uptake Facilitation
12.4.9 Physicochemical Properties Tuning
12.5 Conclusion
References
13: Immunotherapy Against Cancer Stem Cells
13.1 Introduction
13.2 Cancer Stem Cell and Immune System Interactions
13.3 Immune Tumour Microenvironment
13.4 Immune Checkpoints
13.5 Regulatory T Cells
13.6 Dendritic Cells
13.7 Interferons
13.8 Immunotherapy Against CSCs
13.8.1 Adoptive T Cell Therapy
13.8.2 Tumour Infiltrating Lymphocytes and Cancer Stem Cells
13.8.3 T Cell Receptor Therapy and Cancer Stem Cells
13.8.4 Chimeric Antigen Receptor T Cell Therapy and Cancer Stem Cells
13.8.5 Immune Checkpoint Inhibitors
13.8.6 Dendritic Cell-Based Vaccines
13.8.7 Oncolytic Viruses
13.9 Conclusion
References
14: Engineering Nanobody Targeting Cancer Stem Cells
14.1 Introduction
14.2 Nanobody
14.3 Therapeutic Applications of Nanobody
14.3.1 Nb-Based Immunotoxins
14.3.2 Nanobodies as Drug Carriers
14.3.3 Nanobody-Based CAR-T Cells
14.3.4 Nanobodies Targeting Tumor-Associated Receptors
14.4 Nanobodies Targeting Cancer Stem Cells
14.5 Conclusion and Future Perspectives
References
15: Biological Barriers for Drug Delivery to Cancer Stem Cells
15.1 Introduction
15.2 Concept of Biological Barrier
15.3 Consideration of Biological Barriers to Drug Delivery to CSCs
15.4 Extracellular Barriers
15.4.1 Physiochemical Properties of Anticancer Therapeutics
15.4.2 Opsonization and Mononuclear Phagocyte System
15.4.3 Vascular Barrier
15.4.4 Interstitial Fluid Pressure
15.4.5 Tumor Microenvironment (TME) and CSC Niche
15.5 CSC-Specific Barrier
15.5.1 Plasma Membrane
15.5.2 Endosomal Entrapment
15.5.3 Drug Efflux
15.6 Conclusion
References
16: Cancer Stem Cell Markers in Haematological Malignancies
16.1 Introduction
16.2 Cancer Stem Cell Markers in Acute Myeloid Leukaemia
16.3 CD123
16.4 CD33
16.5 CD70
16.6 FLT3
16.7 TIM3
16.8 CLL-1
16.9 IL-1RAP
16.10 CALM/AF10
16.11 Cancer Stem Cell Surface Markers in CML
16.12 CD47
16.13 CD93
16.14 CD25
16.15 CD26
16.16 CD52
16.17 CSCs in Multiple Myeloma
16.18 Conclusion
References
17: Diagnostic and Prognostic Significance of Cancer Stem Cell Surface Markers
17.1 Introduction
17.2 CSC Surface Biomarkers in Human Malignancies
17.3 Diagnostic and Prognostic Significance of CSC Surface Biomarkers
17.4 EpCAM (CD326)
17.5 CD44
17.6 CD133
17.7 CD24
17.8 CD166
17.9 Cancer Stem Cells in Circulation: A Promising Area of Study
17.10 Conclusion
References
18: Diagnostic and Prognostic Implications of Cancer Stem Cell Transcription Factors
18.1 Introduction
18.2 SOX2
18.2.1 Significance in Cancer Diagnosis and Prognosis
18.3 OCT4/POU5F1
18.3.1 Diagnostic and Prognostic Significance
18.4 Nanog
18.4.1 Diagnostic and Prognostic Significance
18.5 KLF4
18.5.1 Diagnostic and Prognostic Significance
18.6 c-Myc
18.6.1 Diagnostic and Prognostic Significance
18.7 Nestin
18.7.1 Diagnostic and Prognostic Significance
18.8 Roles of Stemness Transcription Factors in EMT
18.9 Conclusion
References
19: Diagnostic and Prognostic Significance of Intracellular Markers of CSCs in Patients with Cancers
19.1 Introduction
19.2 Intracellular Markers
19.3 Aldehyde Dehydrogenase (ALDH)
19.4 Breast Cancer
19.5 Colorectal Cancer (CRC)
19.6 Lung Cancer
19.7 Gastric Cancer
19.8 Acute Myeloid Leukemia
19.9 Ovarian Cancer
19.10 Head and Neck Cancer
19.11 Other Cancers
19.12 Sox-2
19.13 Breast Cancer
19.14 Lung Cancer
19.15 Oral Squamous and CRC
19.16 Gastric Cancer
19.17 Oct3/4
19.18 CRC
19.19 Breast Cancer
19.20 HCC (Hepatocellular Cancer)
19.21 Gastric Cancer
19.22 Lung Cancers
19.23 Other Cancers
19.24 Bmi1
19.25 LETM1
19.26 Musashi2
19.27 Sall4
19.28 Co-expression of CSC Markers
19.29 Conclusion
References