ISBN : 9780323913676
Author : Steven Gray
Publisher : Academic Press
Year : 2023
Language : English
Type : Book
Description : Table of contents 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