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Resistance, epigenetics and the cancer ecosystem

Nature Medicine volume 17, pages 288–289 (2011)Cite this article

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Therapeutic resistance is a key roadblock to effective cancer treatment and can occur through various mechanisms. A recent study characterized a previously unknown, reversible mechanism of drug resistance mediated by an altered chromatin state, suggesting that cancer cell populations can use a dynamic strategy to ensure their survival when challenged by therapeutic intervention.

We will never control the most common cancers unless we conquer the overwhelming problem of therapeutic resistance. Resistance blunts the full curative potential of not only standard chemotherapy approaches but also emerging targeted therapies1. Such resistance can occur by multiple mechanisms. A paramount one that has generated the most interest is selection for mutations. This has been a particular problem for resistance to targeted therapies, wherein secondary mutations in initially mutated protein target genes are selected for during treatment; for example, the oncoprotein BCR-ABL2, targeted by imatinib in chronic myelogenous leukemia, and epidermal growth factor receptor (EGFR) mutations in lung cancer, targeted by drugs such as erlotinib3. Mutations that mediate antagonism to drug effects are also a prominent mechanism, such as those that occur in proteins mediating drug efflux, and, for targeted therapies, those that induce increased signaling through alternative survival pathways1.

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Figure 1: Epigenetic modulation of tumor-initiating cells and therapy resistance.

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  1. Stephen B. Baylin is at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, Maryland, USA.,

    Stephen B Baylin

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  1. Stephen B Baylin
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Correspondence to Stephen B Baylin.

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Baylin, S. Resistance, epigenetics and the cancer ecosystem. Nat Med 17, 288–289 (2011). https://doi.org/10.1038/nm0311-288

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