Epigenetics as a mechanism driving polygenic clinical drug resistance
Open accessAbstract
Aberrant methylation of CpG islands located at or near gene promoters is associated with inactivation of gene expression during tumour development. It is increasingly recognised that such epimutations may occur at a much higher frequency than gene mutation and therefore have a greater impact on selection of subpopulations of cells during tumour progression or acquisition of resistance to anticancer drugs. Although laboratory-based models of acquired resistance to anticancer agents tend to focus on specific genes or biochemical pathways, such 'one gene:one outcome' models may be an oversimplification of acquired resistance to treatment of cancer patients. Instead, clinical drug resistance may be due to changes in expression of a large number of genes that have a cumulative impact on chemosensitivity. Aberrant CpG island methylation of multiple genes occurring in a nonrandom manner during tumour development and during the acquisition of drug resistance provides a mechanism whereby expression of multiple genes could be affected simultaneously resulting in polygenic clinical drug resistance. If simultaneous epigenetic regulation of multiple genes is indeed a major driving force behind acquired resistance of patients' tumour to anticancer agents, this has important implications for biomarker studies of clinical outcome following chemotherapy and for clinical approaches designed to circumvent or modulate drug resistance.
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Other studies suggest that some persister phenotypes arise via plasticity induced by drug treatment.
“Meanwhile, other studies suggest that some persister phenotypes arise via plasticity induced by drug treatment [56,64,65].”
From Emerging Insights into Targeted Therapy-Tolerant Persister Cells in Cancer (2021) · cites this paper as [65]
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- Authors
- Glasspool, R. M., Teodoridis, J. M., & Brown, R.
- Affiliations
- Cancer Research UK Scotland Institute (GB)
- Corresponding author
- Brown, R
- Venue
- British Journal of Cancer
- Published
- 2006-02-21
- Volume
- 94
- Issue
- 8
- Pages
- 1087-1092
- ISSN
- 0007-0920 (ISSN-L)
- 1532-1827
- PMC
- PMC2361257
- OpenAlex
- W2085947779
- Cited by
- 236
- References
- 56
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 6 · 2023: 8 · 2022: 7 · 2021: 14 · 2020: 18 · 2019: 8 · 2018: 10 · 2017: 11 · 2016: 15 · 2015: 13 · 2014: 15 · 2013: 17 · 2012: 19
- FWCI
- 1.09
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-sa
- www.springer.com/tdm (unspecified)
- Locations
- British Journal of Cancer (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Keywords
- epigenetics, acquired drug resistance, CpG island methylation, promoter hypermethylation, epimutations, chemosensitivity, tumor progression, gene expression regulation, anticancer agents
- MeSH terms
- Genetics, Humans, CpG Islands, Drug Resistance, Neoplasm, DNA Methylation, Multifactorial Inheritance, Epigenesis, Genetic
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