The cancer epigenome: Concepts, challenges, and therapeutic opportunities
Abstract
Cancer biology is profoundly influenced by changes in the epigenome. Because the dynamic plasticity of the epigenome lends itself well to therapeutic manipulation, the past few years have witnessed an unprecedented investment in the development, characterization, and translation of targeted epigenetic therapies. In this review, I provide a broad context for recent developments that offer a greater understanding of how epigenetic regulators facilitate the initiation, maintenance, and evolution of cancer. I discuss newly developed epigenetic therapies and the cellular and molecular mechanisms that may govern sensitivity and resistance to these agents. I also review the rationale for future combination therapies involving existing and emerging epigenetic drugs.
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Response rates of up to 60% to azacytidine have been reported in MDS.
“Whilst response rates of up to 60% to azacytidine have been reported in MDS 125,129 ,”
From The roles of DNA, RNA and histone methylation in ageing and cancer (2019) · cites this paper as [125]
The prolonged time to initial response, typically around 3 months from treatment onset, is consistent with the primary effects of low dose treatment being mediated via DNA demethylation and epigenetic reprogramming as opposed to direct cytotoxicity.
“The prolonged time to initial response, which typically occurs around 3 months from treatment onset 125 , is consistent with the primary effects of low dose treatment being mediated via DNA demethylation and epigenetic reprogramming as opposed to direct cytotoxicity 126-128 .”
From The roles of DNA, RNA and histone methylation in ageing and cancer (2019) · cites this paper as [125]
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References 73 · Cited by 377
- Authors
- Dawson, M. A.
- Affiliations
- The University of Melbourne (AU)
- Corresponding author
- Dawson, Mark A.
- ORCID
- Dawson, Mark A.
- Venue
- Science
- Published
- 2017-03-17
- Volume
- 355
- Issue
- 6330
- Pages
- 1147-1152
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2596054989
- Cited by
- 377
- References
- 73
- Citations by year
- 2026: 22 · 2025: 28 · 2024: 33 · 2023: 40 · 2022: 54 · 2021: 43 · 2020: 46 · 2019: 52 · 2018: 37 · 2017: 22
- FWCI
- 4.02
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Health and Medical Research Council (1066545, 1085015, 1106444, 1106447)
- Leukaemia Foundation (Fellowship)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
- Keywords
- cancer epigenome, epigenetic regulators, epigenetic drug resistance, combination therapy, epigenetic drugs
- MeSH terms
- Protein Domains, Humans, Isocitrate Dehydrogenase, Mutation, Neoplasms, Transcription, Genetic, Drug Design, DNA Methylation, Chromatin Assembly and Disassembly, Epigenesis, Genetic, Small Molecule Libraries, Molecular Targeted Therapy
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