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Cancer

Drug-tolerant insurgents

Nature volume 464, pages 844–845 (2010)Cite this article

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Some cancer cells that become tolerant to a drug remain resistant even after its withdrawal, yet these cells eventually become sensitive to the drug again. The underlying molecular mechanism is unusual.

The cell population of a tumour is not uniform, the differences arising partly as a result of genetic instability. The prevailing model for how cancer develops is that dominant cell clones in the population survive through Darwinian selection1,2,3. But this clonal selection model is based solely on genetic mutations and, although useful, is overly simplistic. It is not just the accumulation of mutations in cancer-causing genes that drives the lethal properties of cancer4,5. Other factors that contribute to cancer include the regulation of cancer genes by epigenetic means, the self-renewal of potential cancer stem cells, and interactions between tumour cells and their micro-environment2,6. In addition to these intrinsic drivers of cellular proliferation and survival, drug treatments provide further selective pressure, leading to cells becoming drug resistant through both genetic and non-genetic mechanisms7,8.

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Figure 1: Evolution and 'de-evolution' of drug resistance.

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Authors and Affiliations

  1. Paul Workman and Jon Travers are in the Cancer Research UK Centre for Cancer Therapeutics, the Institute of Cancer Research, Haddow Laboratories, Sutton, Surrey SM2 5NG, UK. paul.workman@icr.ac.uk ,

    Paul Workman & Jon Travers

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  1. Paul Workman
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  2. Jon Travers
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Competing interests

Paul Workman is an employee of and Jon Travers a graduate student at the Institute of Cancer Research (ICR), which operates a rewards to inventors scheme. The ICR has an actual or potential commercial interest in inhibitors of chromatin-modifying enzymes, including histone deacetylases and histone demethylases. P.W. is a founder of, Scientific Advisory Board chair of, consultant to, non-executive director of and member of the Board of Directors of Chroma Therapeutics.

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Workman, P., Travers, J. Drug-tolerant insurgents. Nature 464, 844–845 (2010). https://doi.org/10.1038/464844a

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