Epigenetic Cancer Therapy

2nd Edition - May 3, 2023
Editor: Steven Gray
Language: English
Paperback ISBN:
9 7 8 - 0 - 3 2 3 - 9 1 3 6 7 - 6
eBook ISBN:
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 understan… 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.

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
8 Clinical trials
9 Current perspectives and future directions
Conflict of interest
Acknowledgments
Abbreviations
References
Chapter 18. Emerging epigenetic therapies—lysine acetyltransferase inhibitors
Abstract
Chapter outline
1 Introduction
2 Deregulation of KATs in cancer
3 Lysine acetyltransferase: a potential target for therapeutics
4 Conclusion
Abbreviations
Acknowledgments
References
Chapter 19. Epigenetic therapies: histone deacetylases
Abstract
Chapter outline
1 Introduction
2 Histone deacetylases
3 HDACs and cancer
4 HDACi
5 HDACi effects on tumor cells
6 FDA-approved HDACi
7 Why HDACi failed in clinic for the treatment of solid tumors?
8 Short half-life
9 Toxicity
10 Metabolism
11 New perspectives
12 Dual inhibitor compounds
13 Combination with immunotherapies
14 Conclusion
References
Part 4: Issues to overcome/areas of concern
Chapter 20. Epigenetic intratumoral heterogeneity
Abstract
Chapter outline
1 Introduction
2 Using reference-based statistical methods to identify differentially methylated CpGs
3 Using reference-free statistical methods to identify differentially methylated CpGs
4 Statistical methods that identify differentially methylated cell types
5 Conclusion and future perspectives
References
Chapter 21. Challenges for single-cell epigenetic analysis
Abstract
Chapter outline
1 Why single-cell epigenetics?
2 Current single-cell epigenetic assays and associated challenges
3 Applications of single-cell epigenetics in cancer
4 Practical considerations for single-cell epigenetic analysis (and associated challenges)
5 Challenges and unanswered questions in epigenetic research in cancer
6 Concluding remarks
References
Chapter 22. Epigenetics of cisplatin resistance
Abstract
Chapter outline
1 Introduction
2 DNA methylation
3 Epigenetic readers, writers, and erasers and associated links with cisplatin response
4 Noncoding RNAs (ncRNAs)
5 Cancer stem cells and cisplatin resistance
6 The epitranscriptome and cisplatin?
7 Targeting cisplatin resistance epigenetically?
8 Clinical trials
9 Conclusions
Glossary
List of abbreviations
References
Chapter 23. Emerging epigenetic therapies: protein arginine methyltransferase inhibitors
Abstract
Chapter outline
1 Introduction
2 PRMT protein summary
3 The role of PRMT proteins in cancer
4 Discovery and efficacy of PRMT inhibitors
5 Conclusions and future directions
List of abbreviations
References
Part 5: Future directions: translation to the clinic
Chapter 24. Personalized epigenetic therapy—chemosensitivity testing
Abstract
Chapter outline
1 Introduction
2 Chemoresistance in lymphomas
3 Epigenetically encoded chemoresistance
4 The evolving epigenetic landscape of lymphomas: treatment and aging
5 Implementing epigenetic therapy to chemosensitize lymphoma
6 What antitumoral effect to expect from epigenetic drugs?
7 Selecting the right drug for the right patient and vice versa
8 Conclusions
Abbreviations
References
Chapter 25. Epigenetic profiling in cancer: triage, prognosis, and precision oncology
Abstract
Chapter outline
1 Introduction
2 Epigenetics testing in cancer screening and triage
3 Epigenetics profiling for cancer prognosis
4 Epigenetic signatures predict response to treatment
5 Conclusion and further directions
List of abbreviations
References
Chapter 26. Epigenetic priming—fact or falacy?
Abstract
Chapter outline
1 Introduction
2 Epigenetic mechanisms of immune escape
3 Immune “cold” and “hot” tumors
4 Epigenetic therapy to warm up tumors
5 Epigenetic therapy to boost cancer immunity
6 Challenges to epigenetic priming
7 Conclusion
References
Chapter 27. CRISPR, epigenetics, and cancer
Abstract
Chapter outline
1 Introduction
2 DNA methylation/demethylation
3 CRISPR-mediated DNA methylation
4 CRISPR-mediated DNA demethylation
5 Applications of CRISPR-mediated targeted methylation/demethylation in cancer
6 Histone modification
7 CRISPR-mediated histone methylation/demethylation
8 CRISPR-mediated histone acetylation/deacetylation
9 Applications of CRISPR-mediated histone modifications in cancer
10 CRISPR-dCas9-based synthetic transcription factors
11 Limitation and challenges
12 In vivo delivery of CRISPR systems
13 Off-target effects
14 Future perspectives
15 Conclusions
References
Index

Life Sciences

Physical Sciences & Engineering

Social Sciences & Humanities

Health

Epigenetic Cancer Therapy

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Steven Gray