Research ArticleCancer

Inhibition of activin signaling in lung adenocarcinoma increases the therapeutic index of platinum chemotherapy

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Science Translational Medicine  25 Jul 2018:
Vol. 10, Issue 451, eaat3504
DOI: 10.1126/scitranslmed.aat3504

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Blocking activin actively treats cancer

Platinum-based chemotherapy is a mainstay of treatment for lung cancer, but resistance to this therapy is a common problem, as are dose-limiting side effects, particularly kidney toxicity. To search for mechanisms that may contribute to treatment resistance, Marini et al. performed a whole-genome RNA interference screen and identified the activin pathway, which can be targeted. The authors demonstrated that inhibition of this pathway using a small molecule or a protein called follistatin can offer a dual benefit in that it potentiates the effects of platinum drugs in mouse models of cancer and also protects the animals from kidney damage. These findings suggest that activin inhibitors could be a valuable addition to platinum chemotherapy, enhancing the efficacy of treatment while also allowing the use of higher doses or longer periods of drug exposure.