Research ArticleCancer

Off-target toxicity is a common mechanism of action of cancer drugs undergoing clinical trials

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Science Translational Medicine  11 Sep 2019:
Vol. 11, Issue 509, eaaw8412
DOI: 10.1126/scitranslmed.aaw8412

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Drugs may not do what we think they do

The majority of proposed anticancer treatments do not succeed in advancing to clinical use because of problems with efficacy or toxicity, often for unclear reasons. Lin et al. discovered that a drug candidate in clinical development was effective at killing cancer cells even when its target protein was knocked out, suggesting that its proposed mechanism of action was incorrect. The researchers then identified multiple drugs with similar problems and also discovered the correct target for one of them, suggesting that more research and more stringent methods are needed to verify the targets of potential drugs before advancing them to the clinic.

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