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Poised epigenetic states and acquired drug resistance in cancer

Nature Reviews Cancer volume 14, pages 747–753 (2014)Cite this article

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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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Figure 1: Epigenetics of acquired drug resistance.

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Acknowledgements

The authors thank S. Kaye and E. Loomis for comments on the manuscript. The authors' research on epigenetics of drug resistance is supported by grants from Cancer Research UK (A13086) and Ovarian Cancer Action, London, UK.

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  1. Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital Campus, London, W12 0NN, UK

    Robert Brown, Edward Curry, Luca Magnani, Charlotte S. Wilhelm-Benartzi & Jane Borley

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Correspondence to Robert Brown.

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Grants from Cancer Research UK and Ovarian Cancer Action, which is acknowledged (R.B.). Patent on histone methyltransferase inhibitors (R.B.). E.C., L.M., C.S.W.-B and J.B. declare no competing interests.

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Supplementary information S1 | Systematic review of the published literature on epigenetic mechanisms involved in drug resistance in clinical studies (PDF 369 kb)

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Brown, R., Curry, E., Magnani, L. et al. Poised epigenetic states and acquired drug resistance in cancer. Nat Rev Cancer 14, 747–753 (2014). https://doi.org/10.1038/nrc3819

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