Epigenetic Cancer Therapy - 1st Edition - ISBN: 9780128002063, 9780128002247

Epigenetic Cancer Therapy

1st Edition

Editors: Steven Gray
eBook ISBN: 9780128002247
Hardcover ISBN: 9780128002063
Imprint: Academic Press
Published Date: 1st June 2015
Page Count: 748
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Description

Epigenetic Cancer Therapy unites issues central to a translational audience actively seeking to understand the topic. It is ideal for cancer specialists, including oncologists and clinicians, but also provides valuable information for researchers, academics, students, governments, and decision-makers in the healthcare sector.

The text covers the basic background of the epigenome, aberrant epigenetics, and its potential as a target for cancer therapy, and includes individual chapters on the state of epigenome knowledge in specific cancers (including lung, breast, prostate, liver).

The book encompasses both large-scale intergovernmental initiatives as well as recent findings across cancer stem cells, rational drug design, clinical trials, and chemopreventative strategies. As a whole, the work articulates and raises the profile of epigenetics as a therapeutic option in the future management of cancer.

Key Features

  • Concisely summarizes the therapeutic implications of recent, large-scale epigenome studies, including the cancer epigenome atlas
  • Discusses targeted isoform specific versus pan-specific inhibitors, a rational drug design approach to epigenetics relevant to pharmacoepigenetic clinical applications
  • Covers new findings in the interplay between cancer stem cells (CSCs) and drug resistance, demonstrating that epigenetic machinery is a candidate target for the eradication of these CSCs

Readership

Researchers in molecular biology, genetics, and clinical therapy who are interested in the role of epigenetics in cancer biology or those seeking novel means to treat cancer.

Table of Contents

  • List of Contributors
  • Chapter 1. Introduction
    • 1 Introduction to the Area (Key Concepts)
    • 2 Epigenetics and Cancer
    • 3 Targeting Aberrant Epigenetics
    • 4 Issues to Overcome/Areas of Concern
    • 5 Future Directions: Translation to the Clinic
    • References
  • Part 1: Introduction and Key Concepts
    • Chapter 2. DNA Methylation and Hydroxymethylation in Cancer
      • 1 Introduction
      • 2 Epigenetics
      • 3 DNA Methylation Patterns in Cancer
      • 4 Aberrations of Enzymes Involved in DNA Methylation Homeostasis in Cancer
      • 5 DNA Hydroxymethylation in Cancer
      • 6 Conclusion
      • References
    • Chapter 3. Writers, Readers, and Erasers of Epigenetic Marks
      • 1 Introduction
      • 2 Writers
      • 3 Readers
      • 4 Erasers
      • 5 Interactions between the Various Components
      • 6 Epigenetics and Cancer
      • 7 Epigenetic Proteins as Therapeutic Targets
      • 8 Conclusion and Future Opportunities
      • References
    • Chapter 4. MicroRNAs and Cancer
      • 1 miRNA Biogenesis and Functionality
      • 2 miRNAs in Cancer Biology
      • 3 miRNA: An Epigenetic Perspective
      • 4 miRNA Epigenetic Therapy
      • 5 Future Perspectives
      • Acknowledgments
      • References
    • Chapter 5. Long Noncoding RNAs and Cancer
      • 1 Introduction
      • 2 Classification and Nomenclature of lncRNAs
      • 3 Mechanisms of lncRNA Function
      • 4 lncRNAs and Human Disease
      • 5 Methods for Studying lncRNA Expression
      • 6 Strategies for Manipulating lncRNA Expression
      • 7 Conclusions
      • References
    • Chapter 6. Ribosomal RNA Methylation and Cancer
      • 1 Introduction
      • 2 Overview of Human Ribosome Biogenesis: An Intense Energy Consuming Process
      • 3 Transcriptional and Epigenetic Deregulation of rDNA Gene Expression in Cancer
      • 4 Chemical Modifications of rRNA
      • 5 Function of rRNA Methylation
      • 6 Modification of rRNA Methylation in Cancer
      • 7 Concluding Remarks
      • References
    • Chapter 7. Mining the Epigenetic Landscape: Surface Mining or Deep Underground
      • 1 Introduction
      • 2 Summary of Epigenomic Profiling Methods and the Data Generated by Large-Scale Epigenomic Projects
      • 3 Current Tools and Analyses That Can Extend Our Insights into Epigenetic Aberrations in Cancer
      • 4 Conclusion
      • References
  • Part 2: Epigenetics and Cancer
    • Chapter 8. Development of Epigenetic Targeted Therapies in Hematological Malignancies: From Serendipity to Synthetic Lethality
      • 1 Introduction
      • 2 The Methylome in Hematologic Malignancy
      • 3 Hypomethylating Agents: The Strange But True History of the Early Development of Azanucleosides in MDS
      • 4 Azacitidine: The Birth of “Epigenetic” Therapies
      • 5 Is There a Correlation Between Methylation and Response to Hypomethylating Agents?
      • 6 What Is the Optimal Dosing Regimen?
      • 7 HDAC Inhibitors
      • 8 Combination Therapies
      • 9 Azanucleosides as Immunomodulators
      • 10 Targeted Therapeutics with Major Epigenetic Impact: The Next Generation
      • 11 Conclusion
      • References
    • Chapter 9. Epigenetic Therapy in Lung Cancer and Mesothelioma
      • 1 Introduction
      • 2 Overview of Lung Cancer
      • 3 Lung Cancer as an Epigenetic Disease
      • 4 Additional Epigenetic Regulatory Proteins
      • 5 Epigenetic Targeting of Lung Cancer
      • 6 Overview of Malignant Pleural Mesothelioma
      • 7 Malignant Pleural Mesothelioma as an Epigenetic Disease
      • 8 Epigenetic Targeting in Malignant Pleural Mesothelioma
      • 9 Conclusion
      • References
    • Chapter 10. Breast Cancer Epigenetics
      • 1 Introduction
      • 2 DNA Methylation and Breast Cancer
      • 3 The Role of Histone Deacetylases in Breast Cancer
      • 4 Histone Modifications
      • 5 The Role of microRNAs in Breast Cancer
      • 6 Breast Cancer Epigenetic Treatment
      • 7 Conclusion
      • Acknowledgment
      • References
    • Chapter 11. Therapeutic Applications of the Prostate Cancer Epigenome
      • 1 Introduction to Prostate Cancer
      • 2 A Snapshot of the PROSTATE CANCER Epigenome
      • 3 Epigenetic Influences on the Androgen Signaling Axis
      • 4 Drugging the Methylome for the Treatment of CRPC
      • 5 HDAC Inhibitors for the Treatment of CRPC
      • 6 Targeting AR Signaling by Epigenetic Drugs
      • 7 Chemoprevention and Neutraceutical Therapies
      • 8 Future Directions
      • Acknowledgments
      • References
    • Chapter 12. Liver Cancer (Hepatocellular Carcinoma)
      • 1 Liver Cancer: Epidemiology and Risk Factors
      • 2 Current Treatment of HCC
      • 3 Epigenetics
      • 4 Histone Modification
      • 5 Characterization of Classic HDACs
      • 6 HDACS and Cancer
      • 7 HDAC Inhibitors
      • 8 Anticancer Effects of HDAC Inhibitors
      • 9 Endoplasmic Reticulum Stress
      • 10 ER Stress and Cancer
      • 11 ER Stress and HDACs
      • 12 HDAC Inhibitors in Treatment of HCC
      • 13 DNA Methylation in HCC
      • 14 Other Epigenetic Regulatory Proteins
      • 15 ncRNAs
      • 16 Conclusion
      • References
    • Chapter 13. Neuroblastoma
      • 1 Neuroblastoma
      • 2 Epigenetic Changes
      • 3 Epigenetic Targeting Agents
      • 4 miRNA-Based Therapeutics
      • References
    • Chapter 14. The Epigenetics of Medulloblastoma
      • 1 Introduction
      • 2 Medulloblastoma Subtypes
      • 3 Epigenetic Enzymes HDACs and HATs as Targets in Medulloblastoma
      • 4 HDAC Inhibitors as Medulloblastoma Therapeutics
      • 5 Methyltransferases in Medulloblastoma
      • 6 Epigenetic Readers in Medulloblastoma
      • 7 Established Kinases May Also Be Epigenetic Regulators in Medulloblastoma
      • 8 The Intersection of the Ubiquitin Proteasome Pathway and the Epigenetic Pathway in Medulloblastoma
      • 9 MicroRNAs as Medulloblastoma Targets
      • 10 Drug Discovery Considerations in Medulloblastoma
      • 11 Conclusions
      • Acknowledgments
      • References
    • Chapter 15. Clinical Significance of Epigenetic Alterations in Glioblastoma
      • 1 Introduction
      • 2 Intertumoral and Intratumoral Heterogeneity of GBM
      • 3 Aberrant DNA Methylation in GBM
      • 4 Aberrant Histone Modifications and Chromatin Remodeling in GBM
      • 5 Contribution of GSC to GBM Formation and Progression
      • 6 Mechanism of Establishment of H3K27me3 Landscape During GSC Differentiation
      • 7 Novel Treatment Strategy for GBM
      • Acknowledgments
      • References
    • Chapter 16. Esophageal Cancer
      • 1 Introduction
      • 2 DNA Methylation
      • 3 Dysregulation of miRNA
      • 4 Opportunities to Epigenetically Target Esophageal Cancer
      • 5 Other Epigenetic Events in Esophageal Cancer
      • References
    • Chapter 17. Nasopharyngeal Cancer
      • 1 Introduction
      • 2 DNA Hypermethylation in NPC
      • 3 Histone Modifications in NPC
      • 4 MicroRNA Alterations in NPC
      • 5 Long Noncoding RNAs in NPC
      • 6 Clinical Trials
      • 7 Future Perspectives
      • References
  • Part 3: Targeting Aberrant Epigenetics
    • Chapter 18. Nutritional Epigenetic Regulators in the Field of Cancer: New Avenues for Chemopreventive Approaches
      • 1 Introduction
      • 2 Overview of the Cancer Epigenome
      • 3 Dietary Factors and Their Influence on Epigenetics: Avenue for Dietary Intervention to Prevent Cancer
      • 4 Conclusions and Critical Considerations
      • Acknowledgments
      • References
    • Chapter 19. Emerging Epigenetic Therapies—Lysine Methyltransferase/PRC Complex Inhibitors
      • 1 Introduction
      • 2 PRC2 Structure–Function and Drugability
      • 3 Role of PRC2 in Cancer and EZH2 as a Drug Target
      • 4 Discovery of Inhibitors of EZH2/PRC2
      • 5 Conclusions
      • References
    • Chapter 20. Inhibitors of Jumonji C-Domain Histone Demethylases
      • 1 Introduction: Histone Methylation—Normal and Pathological Functions
      • 2 The First Histone Demethylases: LSD1 and LSD2
      • 3 The Jumonji C-Domain Histone Demethylases
      • 4 Role of JMJC Histone Demethylases in Human Cancer
      • 5 Small Compound Inhibitors of JMJC Histone Demethylases
      • 6 Conclusion
      • References
    • Chapter 21. Emerging Epigenetic Therapies: Lysine Acetyltransferase Inhibitors
      • 1 Introduction
      • 2 Aberrant Histone Acetylation Patterns in Diseases
      • 3 Role of KATs in Cancer
      • 4 Lysine Acetyltransferases as Potential Therapeutic Targets
      • 5 Conclusion and Perspective
      • References
    • Chapter 22. Emerging Epigenetic Therapies—Bromodomain Ligands
      • 1 Introduction
      • 2 The Development of BET Bromodomain Ligands
      • 3 BET Bromodomain Ligands in Clinical Trials
      • 4 The Development of CREBBP Bromodomain Ligands
      • 5 The Development of Ligands for Other Bromodomains
      • 6 Conclusion
      • References
    • Chapter 23. Clinical Trials
      • 1 Introduction
      • 2 Single Agent Therapy
      • 3 Combination Therapy
      • 4 Conclusion and Future Perspectives
      • References
  • Part 4: Issues to Overcome/Areas of Concern
    • Chapter 24. Genetic Intratumor Heterogeneity
      • 1 Introduction: Inter- and Intratumor Heterogeneity
      • 2 Genetic ITH as a Result of Population Expansion
      • 3 Cancer from an Evolutionary Perspective
      • 4 Patterns of ITH
      • 5 ITH and the Evolution of Drug Resistance
      • 6 Clinical Implications of ITH
      • Acknowledgments
      • References
    • Chapter 25. Epigenetics Underpinning DNA Damage Repair
      • 1 Introduction
      • 2 Epigenetic Changes in Chromatin
      • 3 DNA Damage
      • 4 DNA Repair Pathways
      • 5 Epigenetic Modifications of Double-Strand Break Repair
      • 6 Chromatin Remodeling Factors Recruited to Sites of DNA Damage
      • 7 DNA Repair in Heterochromatin
      • 8 Conclusion
      • References
    • Chapter 26. Epigenetics of Cisplatin Resistance
      • 1 Introduction
      • 2 DNA Methylation
      • 3 Epigenetic Readers, Writers, and Erasers
      • 4 Noncoding RNAs
      • 5 Histone Variants
      • 6 Cancer Stem Cells and Cisplatin Resistance
      • 7 Protein PTMs Associated with Development of Cisplatin Resistance
      • 8 Targeting Cisplatin Resistance Epigenetically
      • 9 Clinical Trials
      • 10 Conclusion
      • References
    • Chapter 27. Therapeutically Targeting Epigenetic Regulation of Cancer Stem Cells
      • 1 Principles of Stem Cell Biology
      • 2 Cancer and Cancer Stem Cells
      • 3 Epigenetic Regulation of CSC SR and Differentiation
      • 4 Therapeutic Targeting of CSCs
      • 5 Perspective: CSCs and the Future of Cancer Therapeutics
      • References
  • Part 5: Future Directions: Translation to the Clinic
    • Chapter 28. Personalized Epigenetic Therapy—Chemosensitivity Testing
      • 1 Introduction
      • 2 Chemoresistance in Lymphomas
      • 3 Epigenetically Encoded Chemoresistance
      • 4 Implementing Epigenetic Therapy to Chemosensitize Lymphoma
      • 5 What Antitumoral Effect to Expect from Epigenetic Drugs?
      • 6 Selecting the Right Drug for the Right Patient and Vice Versa
      • 7 Resistance to Epigenetic-Acting Drugs and Chemosensitivity Testing
      • 8 Conclusion
      • References
    • Chapter 29. Personalized Therapy—Epigenetic Profiling as Predictors of Prognosis and Response
      • 1 Epigenetic Biomarkers for Precision Medicine
      • 2 Systems Epigenomics for Biomarker Discovery
      • 3 Epigenetic Biomarkers for Diagnosis, Prognosis, and Drug Response
      • 4 Genetic Alterations in Epigenetic Modifiers: Potential Drug Targets
      • 5 Future Perspective of Biomarker Discovery and Application
      • References
  • Index

Details

No. of pages:
748
Language:
English
Copyright:
© Academic Press 2015
Published:
Imprint:
Academic Press
eBook ISBN:
9780128002247
Hardcover ISBN:
9780128002063

About the Editor

Steven Gray

Affiliations and Expertise

Senior Clinical Scientist & Adjunct Assistant Professor, Thoracic Oncology Research Group, Trinity Centre for Health Sciences, St. James's Hospital, Dublin, Ireland

Reviews

"...a helpful reference for researchers and medical professionals interested in epigenetics...contains many resources that may be useful for readers or guide them to technologies and areas of interest quickly. Score: 84 - 3 Stars" --Doody's