Preface
Acknowledgements
Contents
Editors and Contributors
About the Editors
Contributors
Part I: Basic Background
1: Fighting with Cancer: A Common Man´s Dilemma
1.1 Cancer
1.2 Types and Terminologies
1.3 Some Statistics
1.4 Role of Various Physicians and Nursing Care and the Available Treatment Options
1.4.1 Surgery
1.4.2 Chemotherapy
1.4.2.1 Radiotherapy
1.4.3 Cancer Pain Management and Palliative Care
1.5 Coping with Cancer Diagnosis and Treatments
1.6 Rays of Hope
1.7 Winning and Fighting Cancer
1.8 Conclusion
References
2: Cell Biology and Cell Behavior in Cancer
2.1 Introduction
2.1.1 Eukaryotic Cell Structure
2.1.1.1 Cell Membrane
2.1.1.2 Cytoplasm
Organic Molecules
Organelles
Organelles with Double Membranes
NucleusNucleus
Nuclear MembraneNuclear Membrane
NeoplasmNeoplasm
NucleolusNucleolus
ChromosomeChromosome
MitochondrionMitochondrion
ChloroplastsChloroplasts
Organelles with Single Membrane
PeroxisomePeroxisome
Endoplasmic ReticulumEndoplasmic Reticulum
Golgi ApparatusGolgi Apparatus
LysosomeLysosome
2.1.2 Cell Cycle
2.1.2.1 Basic Structure of DNA and Its Function
2.1.2.2 Eukaryotic Chromosome
2.1.2.3 Replication and Repairing of DNA
2.1.2.4 DNA Recombination
2.1.2.5 DNA Transcription
2.1.2.6 Cell Division
Mitosis
Meiosis
2.1.2.7 Basics of Heredity
2.1.2.8 Intracellular Signaling
2.2 Introduction to Cancer Biology
2.2.1 Factors Playing Behind Cancer
2.2.2 Hallmarks of Cancer
2.2.3 Classification of Cancer
2.2.4 Cancer Detection and Diagnosis
2.3 Conclusion
References
3: Tumor Biology: An Introduction
3.1 Introduction: Cancer Perspective from Fundamental Biology
3.2 The Nature of Cancer and Its Types
3.3 Environmental Insults-Mutagens, Carcinogens, and Cancer-Causing Mutations
3.4 Infectious Agents, Inflammation, and Cancer
3.5 Cellular and Genetic Basis of Cancer
3.5.1 Comparison of Cancer Cell and Normal Cell
3.5.2 Genetic View of Cancer
3.5.3 Tumorigenesis
3.5.4 Oncogenes and Tumor Suppressor Genes
3.5.5 Genome-Wide Approach
3.6 Temporal Variation of Cancer Incidence Rate in Different Populations
3.7 Prevention and Early Detection
3.8 Conclusion
References
4: Role of Angiogenesis in Tumors
4.1 Introduction
4.2 Mechanisms of Angiogenesis
4.2.1 Angiogenesis from Endothelial Precursor Cells (EPCs)
4.2.2 Angiogenic Switch
4.3 Angiogenesis in Physiologic Processes
4.4 Angiogenesis in the Pathogenesis of Cancer
4.5 Angiogenesis: A Network of Signaling Pathways
4.5.1 Endogenous Pro-angiogenic Factors
4.5.2 VEGF
4.6 Angiogenesis Ahead of VEGF/VEGFR Pathway
4.6.1 Platelet-Derived Growth Factor (PDGF)/PDGFR
4.6.2 Fibroblast Growth Factor (FGF)/FGFR
4.6.3 Angiopoietins (Ang)/Tie2
4.6.4 Hepatocyte Growth Factor (HGF)/MET
4.7 Inhibitors of Angiogenesis
4.7.1 Angiostatin
4.7.2 Endostatin
4.7.3 Thrombospondins (TSPs)
4.8 Angiogenesis and Cancer
4.8.1 Anti-Angiogenic Treatment of Cancer
4.9 Combinatorial Targeting of Multiple Pro-angiogenic Pathways: An Alternative to Overcome Resistance
4.10 Current and Emerging Multi-Targeting Anti-Angiogenic Agents
4.11 Our Research Endeavors
4.12 Conclusions
References
5: Biology, Chemistry, and Physics of Cancer Cell Motility and Metastasis
5.1 Introduction
5.2 Biological Background
5.2.1 Equilibrium in Cell Population
5.2.2 Oncogene and Tumor Suppressor Genes
5.2.3 Cellular Adhesion
5.2.4 Cell Signaling
5.3 Cancer Cell Motility and Metastasis: Biology and Chemistry
5.3.1 Cancer Cell Motility
5.3.1.1 RhoGTPase Family
5.3.1.2 Single Cell Motility
5.3.1.3 Motility of Collective Cells
5.3.2 Metastasis
5.3.2.1 Proteolytic Enzymes
5.3.2.2 Adhesion Proteins
5.4 Physical and Mechanical Processes in Cell Motility and Metastasis
5.4.1 Physical Interaction in Cell Motility
5.4.2 Cellular Mechanics in Intravasation
5.4.3 Forces Acting on the Circulating Tumor Cells
5.4.4 Extravasation of Circulating Tumor Cells
5.4.4.1 Receptor-Ligand Interactions of Circulating Tumor Cells
5.4.4.2 Physics behind the Location of Metastatic Site
5.5 Conclusions
Appendix
Biological Notes
References
Part II: Diagnostics and Theory
6: MRI, CT, and PETSCAN: Engineer´s Perspective
6.1 Introduction
6.2 Tomographic Imaging in Medical Diagnosis: Historical Developments
6.3 Magnetic Resonance Imaging (MRI)
6.3.1 The Machine: A Gigantic Chamber
6.3.2 Magnetic Moment
6.3.3 Nuclear Magnetic Moment
6.3.4 Classical Precession
6.3.5 Total Magnetization
6.3.6 Radiofrequency Pulse: Related Magnetization
6.4 MR Signal Detection
6.4.1 MR Signal Intensity
6.4.2 Relaxation: Spin-Lattice (T1) and Spin-Spin (T2)
6.4.3 Magnetic Gradient Coils
6.4.4 K-Space and Image Formation
6.4.5 Pulse Sequence
6.5 Computed Tomography
6.5.1 Basics of X-ray
6.5.2 Diagnostic Application of Radiography
6.5.3 Limitations of Radiography
6.6 Basic Principle of Computed Tomography
6.6.1 Image Viewing System
6.7 Components of CT Scanner
6.7.1 X-Ray Detector and Data Acquisition System
6.8 Reconstruction of CT Image
6.9 Evolution of CT Scanning Technology
6.9.1 First-Generation CT (Translate-Rotate Mode)
6.9.2 Second-Generation CT (Multidetector Translate-Rotate Mode)
6.9.3 Third-Generation CT (Rotate-Rotate Mode)
6.9.4 Fourth-Generation CT (Fixed-Rotate)
6.9.5 Electron Beam CT (Fixed-Fixed)
6.9.6 Helical CT
6.10 Clinical Application of CT Scan Image
6.11 PET Scan
6.12 PET Scan: Basic Principle
6.12.1 PET Scan Utilities
6.12.2 Early Detection of Malignant Tumors/Cancers
6.13 Conclusion
References
7: Diffusion, MRI, and Cancer Diagnosis: Physicist´s Outlook
7.1 Introduction
7.2 Diffusion
7.2.1 Phenomenological Notion and Fick´s Laws of Diffusion
7.2.2 Molecular Backgrounds of Diffusion and Random Walk Model
7.2.3 Self-Diffusion
7.2.3.1 Self-Diffusion and Einstein´s MSD Relation
7.2.4 Anisotropic Self-Diffusion
7.3 MRI
7.3.1 NMR in the Context of MRI
7.3.1.1 Relaxation Effects
7.3.1.2 The Bloch Equation and Time Evolution of Bulk Magnetization
7.3.1.3 An Outline of the Basic Pulsed-NMR Experiment
7.3.1.4 Signal-to-Noise Ratio (SNR)
7.3.1.5 FID Signal s(t) to NMR Spectrum S(Omega) and Fourier Transformation
7.3.1.6 Measurements of Relaxation Times
7.3.1.7 Inverse Recovery (IR) Method for Measuring T1
7.3.1.8 Spin-Echo (SE) Method and Measurement of T2
7.3.1.9 Effects of Diffusion on Spin-Echo Signal
7.3.2 NMR Imaging: MRI
7.3.2.1 MRI of Our Body Organs
7.3.2.2 The Gradient Pulses
7.3.2.3 The Receiver or Detector System´´ of an MRI Unit
7.3.2.4 Image Contrast
7.3.2.5 Basic Components of a Standard MRI System
7.3.3 Diffusion MRI
7.3.3.1 Diffusion-Weighted Imaging (DWI)
7.3.3.2 The Stejskal and Tanner´s Pulsed-Field Gradient Spin-Echo (PFG-SE) Sequence
7.3.3.3 Apparent Diffusion Coefficient Mapping (ADC Mapping): Quantitative Analysis with DWI
7.3.3.4 High-Speed Diffusion Imaging: Use of Echo-Planar Imaging (EPI)
7.3.3.5 Diffusion Tensor Imaging (DTI)
7.3.3.6 Indices of Anisotropic Diffusion
7.3.3.7 Application Potential of DTI
7.4 Cancer
7.4.1 Interpretation of DWI and Its Assessment
7.4.2 Clinical DWI in the Body: Some Technical Issues
7.4.3 Applications of DWI-ADC Mapping of Target Organs
7.4.3.1 Detection of Tumors
7.4.3.2 Characterization of Tumors
7.4.4 Distinguishing Tumors from Non-Tumors
7.4.4.1 Monitoring Treatment Response
7.4.4.2 Predicting Treatment Response
7.5 Conclusions
Appendix
References
8: Oncology: Radiation Oncologist´s View
8.1 Introduction
8.1.1 Historical Perspectives
8.2 Mechanism of Action of Radiation and the Biological Basis of Radiation Therapy
8.2.1 DNA Damage
8.2.2 Biological Basis for Radiation Therapy
8.3 Principles of Radiotherapy
8.4 Types of Radiation
8.4.1 Ionising Radiation
8.4.2 Ionising Electromagnetic Radiation
8.4.3 X-Rays
8.4.4 Gamma (γ) Rays
8.4.5 Ionising Particulate Radiation
8.5 Units Used in Radiation Oncology
8.6 Basics of Radiation Protection
8.7 Techniques of Radiotherapy
8.7.1 Conventional Radiotherapy (2D Technique)
8.7.2 Three-Dimensional Conformal Radiation Therapy (3DCRT)
8.7.2.1 The Planning Process of 3DCRT
8.7.3 IMRT: Intensity-Modulated Radiation Therapy (IMRT)
8.7.3.1 Planning System of IMRT
8.7.4 Image-Guided Radiation Therapy (IGRT)
8.7.4.1 Rationale for Image-Guided Radiation Therapy
8.7.5 Stereotactic Radiosurgery and Radiotherapy (SRS and SRT)
8.7.6 Volumetric Modulated Arc Therapy (VMAT)
8.7.7 Surface-Guided Radiation Therapy (SGRT)
8.7.8 Brachytherapy
8.8 Fractionation in Radiotherapy
8.8.1 Types of Fractionation in Radiotherapy
8.9 Side Effects of Radiation
8.9.1 Early Effects (Acute Effects)
8.9.2 Late Effects
8.10 Conclusions
References
9: Oncology: Biochemists´ Perspective
9.1 Introduction
9.2 Causes of Cancer
9.3 Development of Cancer
9.3.1 Initiation
9.3.2 Promotion
9.3.3 Progression
9.4 Molecular Pathways Associated with Cancer
9.4.1 Cell Fate
9.4.1.1 Stem Cell Self-Renewal Pathway
WNT Pathway
Hedgehog (Hh) Pathway
Notch Pathway
BMI Pathway
9.4.1.2 Chromatin Modification
9.4.2 Cell Survival
9.4.2.1 Alteration of Cell Cycle
9.4.2.2 Alteration of Apoptosis Pathway
9.4.3 Genome Maintenance
9.4.4 Molecular Stress Pathway
9.5 Cancer Biomarkers
9.6 Molecular Therapy of Cancer
9.7 Cancer Chemoprevention
9.8 Conclusion
Appendix
References
10: Oncology: Pathologist´s View
10.1 Introduction
10.2 Oncology, Neoplasia, and Cancer
10.3 Risk Group for Developing Cancer
10.4 Carcinogenesis
10.5 Cell Cycle Regulators and their Role in Cancer
10.6 Carcinogenesis Model
10.7 Evolution and Cancer
10.8 Cancer Stem Cells
10.9 Cancer Stem Cells and Growth of Cancer
10.10 Pathologist in Diagnosis of Cancer
10.11 Histopathology Techniques in Biopsy Interpretation
10.12 Final Diagnosis by a Pathologist
10.13 Molecular Profiling of Tumors: The Future of Cancer Diagnostics
References
Part III: Cancer Therapeutics
11: Surgical Oncology: An Overview
11.1 Introduction
11.2 Evolution of Role of Surgery in Oncology
11.3 Role of Surgical Oncologist
11.3.1 Cancer Screening
11.3.2 Diagnosis and Staging
11.4 Staging
11.5 Surgery: From More, to Less, to None
11.6 Plastic and Reconstructive Surgery
11.7 Minimally Invasive Surgery (MIS)
11.8 Role of Robotic Surgery
11.9 Impact of Emerging Technology in Surgical Oncology
11.10 Expanding Indications of Treatment and Indian Context
11.11 Conclusion
References
12: Medical Oncology in Cancer Treatment
12.1 Introduction
12.2 History (DeVita and Chu 2008)
12.3 Chemotherapeutic Drug: Its Evolution and Development
12.4 Indications of Chemotherapy
12.5 Cell Biology and Chemotherapy
12.6 Types of Systemic Therapy and Its Functions
12.6.1 Cell Cycle Nonspecific Chemotherapy
12.6.1.1 Alkylating Agents
12.6.1.2 Antitumor Antibiotics
12.6.2 Cell Cycle Specific Chemotherapy
12.6.2.1 Hormonal Agents
12.6.2.2 Biological Response Modifiers
12.6.2.3 Targeted Therapy
12.6.2.4 Immunotherapy
12.6.2.5 Gene Therapy
12.7 Drug Resistance
12.8 Conclusion
References
13: Chemotherapy Effects on Immune System
13.1 Introduction
13.2 The Immune System and Cancer
13.3 Anticancer Immune Surveillance
13.4 Clinical Scenario for Use of Chemotherapeutic Agents
13.5 Conventional Cancer Chemotherapeutic Agents
13.6 Immunological Effects of Commonly Used Cancer Chemotherapeutic Drugs
13.6.1 Other Uses of Cancer Chemotherapeutic Agents
13.7 Toxicity of Conventional Anticancer Drugs on Immune System
13.8 Targeted Cancer Chemotherapy
13.9 Immunological Effects of Targeted Anticancer Agents
13.10 Conclusion
References
14: Telomerase and Its Therapeutic Implications in Cancer
14.1 Introduction
14.2 Telomere Structure and Function
14.3 Telomeric Proteins
14.4 Telomere and Mechanism of Cellular Mortality
14.5 Structure and Function of Telomerase
14.6 Implications of Telomerase in Cancer
14.6.1 Role of Gene Amplification and Rearrangements
14.6.2 Role of Promoter Mutations in hTERT Regulation
14.6.3 Role of Promoter Methylation in hTERT Regulation
14.6.4 Role of MicroRNAs in hTERT Regulation
14.7 Therapeutic Implications of Telomerase in Cancer
14.7.1 Polyphenols
14.7.2 Alkaloids
14.7.3 Terpenes
14.7.4 Xanthones
14.7.5 Currently Used Inhibitors of Telomerase
14.8 Conclusion
References
15: Pain Management in Oncology
15.1 Introduction and Epidemiology
15.2 Assessment of Performance
15.2.1 Assessment of Performance Status
15.2.2 Assessment of Pain Intensity
15.3 Evaluation of the Patient with Cancer Pain
15.3.1 History of the Malignancy
15.3.2 Pain History
15.3.3 General History
15.3.4 Cancer Pain Syndromes
15.3.4.1 Bone Pain Syndrome
Mechanism of Bone Pain
Investigation
Management
15.3.4.2 Back Pain Syndrome
15.3.4.3 Degenerative Disk Disease and Neoplastic Disease
Causes of Neoplastic Disease
Investigations
Management
Pain Due to Direct Tumor Involvement of Nerve
Epidural Spinal Cord and Cauda Equine Compression
15.3.4.4 Base of Skull Disease Syndrome
15.3.4.5 Postsurgical Syndromes
15.3.4.6 Postradiotherapy Pain Syndromes
15.3.4.7 Postchemotherapy Pain Syndrome
15.3.4.8 Neuropathic Pain
15.4 Management of Pain
15.4.1 Antineoplastic Treatment
15.4.2 Pharmacologic Management
15.4.2.1 Drugs
Routes of Administration
Opioid Medicines
Morphine in Children
Signs of Morphine Toxicity
Management of Morphine Toxicity
Transdermal Fentanyl
Oral Transmucosal Fentanyl Citrate (OTFC)
15.4.2.2 Weak Opioids
15.4.2.3 Adjuvants
15.5 Interventional Pain Management
15.5.1 Radio-Frequency Ablation
15.5.2 Intrathecal Saddle Neurolysis
15.5.2.1 Advanced Interventional Pain Management Procedures
15.5.2.2 Peripheral Nerve Stimulation
15.5.2.3 Vertebroplasty and Balloon Kyphoplasty (McCall et al. 2008)
15.5.2.4 Neurosurgical Palliative Techniques
15.5.2.5 Pituitary Ablation
15.5.2.6 Commissural Myelotomy
15.5.2.7 Percutaneous Cordotomy
15.5.3 Biopsychosocial Model of Pain (Dueñas et al. 2016)
15.5.3.1 Behavioral Pain Management Techniques
15.5.4 Palliative Care
15.6 Hospice-Based and Home-Based Pain Management
15.6.1 Respite Care
15.7 Conclusion
References
Part IV: Emerging Trends in Cancer Research
16: New Approaches in Cancer Research: Stem Cell Research, Translational Research, Immunotherapy, and Others
16.1 Introduction
16.2 Stem Cell Research
16.2.1 Stem Cell Therapy: A New Messiah against Cancer
16.2.2 Anticancer Applications of Stem Cells
16.2.2.1 Enzyme/pro-Drug Therapy
16.2.2.2 Secretion of Antitumor Agents
16.2.2.3 Use of Viruses
16.2.3 Stem Cells as Regenerative Medicine for Cancer
16.2.4 Factors Governing Success of Stem Cell Therapy
16.2.5 Cancer Stem Cell: A Hero-Turned-Villain?
16.2.6 Therapeutic Approaches against Cancer Stem Cells
16.2.7 Choosing the Right Path
16.3 Translational Research
16.3.1 Basic Research Versus Applied Research
16.3.2 Definition of Translational Research
16.3.3 Translational Research in Cancer Diagnosis and Drug Development
16.4 Immunotherapy in Cancer
16.4.1 Immune Scenario in Cancer
16.4.2 Immunotherapy against Cancer: Enforcing the Immune System in the Right Way
16.4.3 Cell-Based Immunotherapy: Invigorating the Sentinels
16.4.3.1 Whole Tumor Cell Vaccine
16.4.3.2 Dendritic Cells
16.4.3.3 CAR-T Cells
16.4.4 Antibody-Based Immunotherapy: Additional Forces Recruited
16.4.5 Other Modes of Immunotherapy in Practice
16.4.6 Critical Challenges to Counter
16.4.7 Footsteps for Future
16.5 Personalized Therapy
16.6 Concluding Remarks
References
17: Cancer Cell Lines: Its Implication for Therapeutic Use
17.1 Introduction
17.2 Dawn of Cell Culture and the Establishment of First Human Cancer Cell Line
17.3 HeLa Cells and their Usefulness in Developing Tissue Culture Techniques
17.4 MDA-MB-468 Cell Line which Questioned the Histopathology of HeLa Cells
17.5 Denver Episode and Unethical Behavior of a Senior Scientist
17.6 Sexing of Long-Term Cell Lines
17.7 My Meeting with the Legendry Jonas Salk in Lake Placid
17.8 My Interview in Houston by the Senior Documentary Producer of BBC London
17.9 My Breakfast Meeting in Houston with Members of Lacks Family
17.10 Human Breast Cancer Cell Line MCF-7 and its Derivative Sublines
17.11 How the Inflammatory Breast Cancer Cell Lines Became Human Embryonic Kidney Cancer Line (293 HEK): A Detective Story?
17.12 Source of Cell Line Contamination and Authentication
17.13 Recommendations by Eminent Cancer Scientists to the U.S. Secretary of Health
17.14 Use of Cancer Cell Lines in Indian Scenario for Cancer Treatment and Patient Care
17.15 Conclusions
Appendix
References
18: Genomics of Cancer
18.1 Introduction
18.2 Methods in Cancer Genomics
18.3 Cancer Genome Initiatives and Databases
18.4 Mutational Signatures
18.5 Mutation Rate
18.6 Structural Variants
18.7 Copy Number Alterations
18.8 Carcinogenic Pathogens
18.9 Cancer Epigenomics
18.10 Future Directions
References
19: Diabetes and Cancer
19.1 Introduction
19.2 Association between Diabetes and Cancer: What Are the Evidences?
19.3 Increased Cancer Mortality in Diabetes
19.3.1 Possible Biologic Links
19.3.2 Insulin/IGF 1 Axis
19.3.3 Hyperglycaemia and Cancer
19.3.4 Obesity and Cancer
19.3.5 Chronic Inflammation
19.4 Effect of Anti-Diabetic Drugs on Cancer
19.5 Effect of Anticancer Drugs on Glucose Level
19.6 Management of Diabetes in Cancer Patients
19.7 Conclusion
References
20: Oncology Informatics, AI, and Drug Discovery
20.1 Introduction
20.2 Introduction to AI
20.3 Oncology Informatics
20.4 AI-Assisted Drug Discovery
20.5 Conclusions
References
21: Radiomics: Cropping More from the Images
21.1 Introduction
21.2 Radiomics Process Cascade
21.3 Defining the Clinical Problem
21.4 Image Modalities for Radiomics
21.5 Image Acquisition
21.6 Preprocessing of Images
21.7 Lesion Segmentation
21.8 Feature Extraction
21.9 Feature Selection
21.10 Training and Performance Measurement
21.11 Conclusion
References
Part V: Epidemiology and Statistics of Cancer
22: Statistics in Cancer: Diagnosis, Disease Progression, Treatment Efficacy, and Patient Survival Studies
22.1 Introduction
22.2 Types of Studies
22.2.1 Population Level Studies
22.2.2 Prognostic Studies
22.2.3 Individual-Level Studies
22.3 Diagnosis
22.3.1 Method of Diagnosis
22.3.2 The Proposed Method (Statistical Diagnosis)
22.3.2.1 Data Preprocessing
22.3.2.2 Statistical Diagnosis and Cancer Intensity
22.3.2.3 Geometric Mean
22.3.3 Classification
22.3.4 Assessment of Progress
22.3.5 Survival Curve
22.4 Conclusions
Appendix
Statistical Notes
References
23: Epidemiology of Cancer: Asian Perspective Revised
23.1 Introduction
23.2 Epidemiology
23.3 Etiological (Risk) Factors of Cancer
23.4 Cancer Registry
23.5 Prevention
23.6 Warning Signals of Cancer
23.7 Treatment
23.8 Conclusion
References
24: Cancer Genomics and Diagnostics: Northeast Indian Scenario
24.1 Introduction
24.2 Types of Cancers
24.3 Cancer Genomics
24.4 Molecular Diagnostics in Cancer
24.4.1 Head and Neck Cancer
24.4.2 Oral Cancer
24.4.3 Nasopharyngeal Carcinoma
24.4.4 Oesophageal Cancer
24.4.5 Breast Cancer
24.4.6 Colorectal Cancer
24.5 TheP4´´ Medicine
24.5.1 Predictive
24.5.2 Preventive
24.5.3 Personalised
24.5.4 Participatory
24.6 Present and Future Scenario of P4 Medicine in Cancer Treatment
Appendix
References