Book contents
- Frontmatter
- Dedication
- Contents
- List of Contributors
- Preface
- Part 1.1 Analytical techniques: analysis of DNA
- Part 1.2 Analytical techniques: analysis of RNA
- Part 2.1 Molecular pathways underlying carcinogenesis: signal transduction
- Part 2.2 Molecular pathways underlying carcinogenesis: apoptosis
- Part 2.3 Molecular pathways underlying carcinogenesis: nuclear receptors
- Part 2.4 Molecular pathways underlying carcinogenesis: DNA repair
- Part 2.5 Molecular pathways underlying carcinogenesis: cell cycle
- Part 2.6 Molecular pathways underlying carcinogenesis: other pathways
- Part 3.1 Molecular pathology: carcinomas
- Part 3.2 Molecular pathology: cancers of the nervous system
- Part 3.3 Molecular pathology: cancers of the skin
- Part 3.4 Molecular pathology: endocrine cancers
- Part 3.5 Molecular pathology: adult sarcomas
- Part 3.6 Molecular pathology: lymphoma and leukemia
- Part 3.7 Molecular pathology: pediatric solid tumors
- Part 4 Pharmacologic targeting of oncogenic pathways
- 78 Oncology drug discovery for biologics: antibody development strategies and considerations
- 79 Targeting the EGFR family of receptor tyrosine kinases
- 80 Therapeutic approaches with antibodies to cell-surface receptors
- 81 Signal transduction in tumor angiogenesis
- 82 Tyrosine-kinase inhibitors in oncology
- 83 Anti-estrogens and selective estrogen-receptor modulators
- 84 Therapeutic applications of anti-sense mechanisms for the treatment of cancer
- 85 Induction of apoptosis
- 86 DNA-methylation inhibitors
- 87 Histone deacetylase inhibitors
- 88 Drug resistance: as complex and diverse as the disease itself
- 89 Molecular profiling and therapeutic decision-making: the promise of personalized medicine
- 90 DNA repair inhibition in anti-cancer therapeutics
- Index
- References
87 - Histone deacetylase inhibitors
from Part 4 - Pharmacologic targeting of oncogenic pathways
Published online by Cambridge University Press: 05 February 2015
Book contents
- Frontmatter
- Dedication
- Contents
- List of Contributors
- Preface
- Part 1.1 Analytical techniques: analysis of DNA
- Part 1.2 Analytical techniques: analysis of RNA
- Part 2.1 Molecular pathways underlying carcinogenesis: signal transduction
- Part 2.2 Molecular pathways underlying carcinogenesis: apoptosis
- Part 2.3 Molecular pathways underlying carcinogenesis: nuclear receptors
- Part 2.4 Molecular pathways underlying carcinogenesis: DNA repair
- Part 2.5 Molecular pathways underlying carcinogenesis: cell cycle
- Part 2.6 Molecular pathways underlying carcinogenesis: other pathways
- Part 3.1 Molecular pathology: carcinomas
- Part 3.2 Molecular pathology: cancers of the nervous system
- Part 3.3 Molecular pathology: cancers of the skin
- Part 3.4 Molecular pathology: endocrine cancers
- Part 3.5 Molecular pathology: adult sarcomas
- Part 3.6 Molecular pathology: lymphoma and leukemia
- Part 3.7 Molecular pathology: pediatric solid tumors
- Part 4 Pharmacologic targeting of oncogenic pathways
- 78 Oncology drug discovery for biologics: antibody development strategies and considerations
- 79 Targeting the EGFR family of receptor tyrosine kinases
- 80 Therapeutic approaches with antibodies to cell-surface receptors
- 81 Signal transduction in tumor angiogenesis
- 82 Tyrosine-kinase inhibitors in oncology
- 83 Anti-estrogens and selective estrogen-receptor modulators
- 84 Therapeutic applications of anti-sense mechanisms for the treatment of cancer
- 85 Induction of apoptosis
- 86 DNA-methylation inhibitors
- 87 Histone deacetylase inhibitors
- 88 Drug resistance: as complex and diverse as the disease itself
- 89 Molecular profiling and therapeutic decision-making: the promise of personalized medicine
- 90 DNA repair inhibition in anti-cancer therapeutics
- Index
- References
Summary
Introduction
The base sequence of DNA provides the genetic code for proteins. The regulation of expression of genes is largely determined by the structure of the chromatin proteins associated with the DNA. Such epigenetic gene regulation refers to heritable and non-heritable gene expression that occurs without changes in DNA sequence (1–5). DNA is packaged in chromatin, which is structurally complex and dynamic, consisting of DNA, histones, and non-histone proteins (1,2). Nucleosomes are repeating units in chromatin composed of approximately 146 base pairs of two loops of DNA wrapped around an octamer core of pairs of histones H4, H3, H2A, and H2B. Histone amino tails are subject to post-translational modification by acetylation of lysines, methylation of lysines and arginines, phosphorylation of serines, ubiquitination of lysines, sumoylation, proline isomerization, and ADP-ribosylation (3–6). Among enzymes involved in chromatin protein structural modification are histone deacetylases (HDACs) and histone acetyltransferases (HATs), which determine the acetylation of histones and other proteins. Alterations of the structure and/or expression of HDACs and HATs occur in many cancers (7,8). In addition to histones, HDACs and HATs have many non-histone protein substrates that have a role in regulating gene expression, cell proliferation, cell migration, and cell death (8–13).
This chapter will focus on the biological activity of the zinc-dependent HDACs and the development of the HDAC inhibitors (HDACi) to treat cancers.
- Type
- Chapter
- Information
- Molecular OncologyCauses of Cancer and Targets for Treatment, pp. 912 - 920Publisher: Cambridge University PressPrint publication year: 2013
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