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Poised epigenetic states and acquired drug resistance in cancer
Abstract
Epigenetic events, which are somatically inherited through cell division, are potential drivers of acquired drug resistance in cancer. The high rate of epigenetic change in tumours generates diversity in gene expression patterns that can rapidly evolve through drug selection during treatment, leading to the development of acquired resistance. This will potentially confound stratified chemotherapy decisions that are solely based on mutation biomarkers. Poised epigenetic states in tumour cells may drive multistep epigenetic fixation of gene expression during the acquisition of drug resistance, which has implications for clinical strategies to prevent the emergence of drug resistance.
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“This is not surprising, since decades of research on targeted cancer therapy have shown that the majority of patients who respond well to initial treatment develop resistance.57, 58, 59, 60”
From Overcoming Resistance to Drugs Targeting KRAS Mutation (2020) · cites this paper as [59]
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Metadata
- Authors
- Brown, R., Curry, E., Magnani, L., Wilhelm-Benartzi, C. S., & Borley, J.
- Affiliations
- Hammersmith Hospital (GB)
- Corresponding author
- Brown, Robert
- Venue
- Nature Reviews Cancer
- Published
- 2014-09-25
- Volume
- 14
- Issue
- 11
- Pages
- 747-753
- ISSN
- 1474-175X (ISSN-L)
- 1474-1768
- OpenAlex
- W2095124748
- Cited by
- 301
- References
- 96
- Citations by year
- 2026: 4 · 2025: 16 · 2024: 23 · 2023: 21 · 2022: 26 · 2021: 41 · 2020: 37 · 2019: 34 · 2018: 27 · 2017: 23 · 2016: 30 · 2015: 18 · 2014: 1
- FWCI
- 2.29
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature reviews. Cancer (publishedVersion)
- PubMed (publishedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
- Funders
- Cancer Research UK (13086, A13086, 15954)
- 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
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Keywords
- epigenetic heterogeneity, acquired drug resistance, cancer, epigenetic targeting, chemoresistance, gene expression evolution
- MeSH terms
- Animals, Humans, Neoplasms, Gene Expression Regulation, Neoplastic, Drug Resistance, Neoplasm, Epigenesis, Genetic
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