Drugging an undruggable target

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Science  30 Sep 2016:
Vol. 353, Issue 6307, pp. 1510
DOI: 10.1126/science.353.6307.1510-c

Transcription factors have long been viewed as “undruggable” targets for therapy; however, this concept may now need some tweaking. Cho et al. found that a small-molecule drug (PT2399) that inhibits the activity of the transcription factor HIF2α (hypoxia-inducible factor 2α) has promising antitumor effects in mouse models of kidney cancer. HIF2α controls the expression of genes that help tumors cope with low amounts of oxygen. In mice, PT2399 suppressed the growth of metastatic kidney tumors and improved the animals' survival. Not all tumors responded to the drug, suggesting that in a clinical setting, doctors may need to rely on yet-to-be-discovered biomarkers to match the drug with the patients most likely to benefit.

Nature 10.1038/nature19795 (2016).

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