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Epigenetic Cancer Therapy
2nd Edition - May 3, 2023
Editor: Steven Gray
Paperback ISBN:9780323913676
9 7 8 - 0 - 3 2 3 - 9 1 3 6 7 - 6
eBook ISBN:9780323917155
9 7 8 - 0 - 3 2 3 - 9 1 7 1 5 - 5
Epigenetic Cancer Therapy, Second Edition provides a comprehensive discussion of healthy and aberrant epigenetic biology, along with new discoveries to improve our understanding… Read more
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Epigenetic Cancer Therapy, Second Edition provides a comprehensive discussion of healthy and aberrant epigenetic biology, along with new discoveries to improve our understanding of cancer epigenetics and therapeutics. The book encompasses 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. Since the publication of the first edition of this book, the field of epigenetics has undergone significant change. New epigenetic therapies have been designed and approved for clinical use.
Our knowledge of the plasticity of the epigenome in cancer and disease has expanded dramatically, with increasing evidence linking pollution to epigenetic changes in cancer development. This second edition has been fully updated to address these changes, along with promising therapeutic programs such as CRISPR/Cas9 mediated approaches, CAR-T based therapies, epigenetic priming, histone modifications, and similar, transformative advances across synthetic biology and cellular engineering.
Concisely summarizes the therapeutic implications of recent, large-scale epigenome studies
Covers new findings in the interplay between cancer stem cells (CSCs) and drug resistance, thus demonstrating that epigenetic machinery is a candidate target for the eradication of these CSCs
Provides a fully updated resource on new topics, including the epitranscriptome, oncohistones, single cell analysis, epigenetic priming, CRISPR therapy, CAR-T therapy, and epigenetics and pollution
Features chapter contributions from leading experts in the field
Researchers in genetics, molecular biology, oncology, pharmaceutical science, and clinical therapy who are interested in the role of epigenetics in cancer biology or those seeking novel means to treat cancer
Cover image
Title page
Table of Contents
Copyright
List of contributors
Chapter 1. Introduction
Abstract
Chapter outline
1 Introduction
2 Introduction to the area (key concepts)
3 Epigenetics and cancer
4 Targeting aberrant epigenetics
5 Issues to overcome/areas of concern
6 Future directions: translation to the clinic
References
Part 1: Introduction and key concepts
Chapter 2. Methylation and hydroxymethylation in cancer
Abstract
Chapter outline
1 Introduction
2 Epigenetics
3 DNA methylation patterns in cancer
4 Aberrations of enzymes involved in DNA methylation homeostasis in cancer
5 Conclusions
List of abbreviations
References
Chapter 3. Writers, erasers, and readers of DNA and histone methylation marks
Abstract
Chapter outline
1 Introduction
2 DNA methylation writers, erasers, and readers
3 Histone lysine methylation writers, erasers, and readers
4 Arginine methylation writers, erasers, and readers
5 Interplay between different methylation marks
6 Relevance of DNA methylation and histone methylation in cancer
7 Regulators of DNA and histone methylation as therapeutic targets
8 Conclusion
Acknowledgments
List of abbreviations
References
Chapter 4. Oncohistones
Abstract
Chapter outline
1 Introduction
2 Histone H1 in tumorigenesis
3 H2 histone mutations in tumorigenesis
4 H3 histones in tumorigenesis (including histone H3 variants)
5 K27M
6 K36M
7 G34
8 H4 histones in tumorigenesis
9 Oncohistone mimics
10 Can we target oncohistones effectively?
11 Targeting oncohistone-altered pathways
12 Car-T-mediated targeting of oncohistone mutated cancer
13 Role of crispr in targeting oncohistones?
14 Conclusions
References
Chapter 5. microRNA, epi-microRNA, and cancer
Abstract
Chapter outline
1 miRNA biogenesis and functionality
2 miRNA in cancer biology
3 miRNA: an epigenetic perspective
4 miRNA epigenetic therapy
5 Future perspectives
Acknowledgments
List of abbreviations
References
Chapter 6. Long noncoding RNA in human cancers: to be or not to be, that is the question
Abstract
Chapter outline
1 lncRNAs in cancer have come of age
2 Regulation of rRNA biogenesis
3 Regulation of translation in cancer
4 Regulation of translation by lncRNAs
5 Conclusion and perspective
References
Chapter 7. The emerging roles of epitranscriptomic marks in cancer
Abstract
Chapter outline
1 Introduction
2 N6-methyladenosine in cancer
3 A-to-I RNA editing in cancer
4 5-Methylcytosine in cancer
5 N7-methylguanosine in cancer
6 2′-O-methylation in cancer
7 Pseudouridylation in cancer
8 N1-methyladenosine in cancer
9 3-Methylcytidine in cancer
10 Epitranscriptomics in diagnostics and therapeutics
11 Conclusions
List of abbreviations
References
Chapter 8. Epigenomic profiling at genome scale: from assays and analysis to clinical insights
Abstract
Chapter outline
1 Introduction
2 Epigenomic profiling methods and the data generated by large-scale epigenomic projects
3 Tools and analyses
4 Conclusion
References
Chapter 9. Environmental pollution, epigenetics, and cancer
Abstract
Chapter outline
1 Introduction
2 Pollutants
3 Conclusion
References
Chapter 10. Synthetic biology and cell engineering—deriving new insights into cancer epigenetics
Abstract
Chapter outline
1 Introduction: an overview of epigenetic engineering
2 Genetic reporters: synthetic genes to monitor transcriptional regulation
3 Protein reporters: engineered proteins to track chromatin features in cancer cells
4 Epigenome editing: precise modification of chromatin
5 Epigenome actuation: streamlined chromatin-binding regulators of transcription
6 Conclusion
Glossary
Abbreviations
References
PART 2: Epigenetics and cancer
Chapter 11. Epigenetic targeted therapies in hematological malignancies
Abstract
Chapter outline
1 Introduction
2 Methylation as a clinical target in hematological disorders
3 Acetylation as a clinical target in hematological disorders
4 Conclusion
Acknowledgements
References
Chapter 12. Epigenetic therapy in lung cancer
Abstract
Chapter outline
1 Introduction
2 Overview of lung cancer
3 Epigenetic modifications in lung cancer
4 Environmental factors affecting the lung epigenome
5 Epigenetic targeting of lung cancer
6 Intratumor epigenetic heterogeneity and epigenetic therapies
7 Immunotherapy and epigenetics in lung cancer
8 Conclusions
References
Chapter 13. Breast cancer epigenetics
Abstract
Chapter outline
1 Introduction
2 Epigenetic alterations in breast cancer
3 Targeted epigenetic therapies
4 DNMT inhibitors
5 Newer epigenetic modifiers
6 Current status and future directions
Disclosure
Acknowledgements
References
Chapter 14. Therapeutic applications of the prostate cancer epigenome
Abstract
Chapter outline
1 Introduction to prostate cancer
2 A snapshot of the prostate cancer epigeneome
3 Epigenetic modulation of androgen receptor signaling
4 Drugging the methylome for the treatment of castration-resistant prostate cancer
5 HDAC inhibitors for the treatment of castration-resistant prostate cancer
6 Targeting AR signaling by epigenetic drugs
7 Chemoprevention and neutraceutical therapies
8 Conclusion
Acknowledgments
Abbreviations
References
Chapter 15. Neuroblastoma
Abstract
Chapter outline
1 Neuroblastoma
2 Epigenetic changes
3 Epigenetic targeting agents
4 miRNA-based therapeutics
References
Part 3: Targeting aberrant epigenetics
Chapter 16. Epigenetic therapies—update on lysine methyltransferase/PRC complex inhibitors
Abstract
Chapter outline
1 Introduction
2 PRC enzyme mechanisms
3 PRC2 in cancer
4 Synthetic lethality
5 Tumor immunity
6 First-generation EZH2 inhibitors
7 Conformationally constrained EZH2 inhibitors
8 EED-targeted PRC2 modulators
9 EZH2 and EED degraders
10 Covalent EZH2 inhibitors
11 Clinical activity of EZH2 inhibitors
12 Resistance mechanisms to EZH2 inhibition
13 Conclusions
References
Chapter 17. Inhibitors of Jumonji-C domain-containing histone demethylases
Abstract
Chapter outline
1 Jumonji-C domain-containing family of writers
2 Role of JmjC proteins in human cancer
3 Mechanism of inhibition
4 Chemical biology tools for the discovery of JmjC inhibitors
5 Development of selective inhibitors
6 JmjC inhibitors in cancer therapy
7 JmjC-based combinatorial approaches and drug resistance
Steven Gray is a Senior Clinical Scientist and Adjunct Assistant Professor in the Thoracic Oncology Research Group, Trinity Centre for Health Sciences at St. James's Hospital, Dublin, Ireland.
Affiliations and expertise
Senior Clinical Scientist and Adjunct Assistant Professor, Thoracic Oncology Research Group, Trinity Centre for Health Sciences, St. James's Hospital, Dublin, Ireland