Research ArticleCancer

Repression of BET activity sensitizes homologous recombination–proficient cancers to PARP inhibition

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Science Translational Medicine  26 Jul 2017:
Vol. 9, Issue 400, eaal1645
DOI: 10.1126/scitranslmed.aal1645

BET-ting on a new drug combination

PARP inhibitors are drugs that interfere with DNA repair, particularly in cancers with defects in homologous recombination. To identify drugs that may potentiate the activity of PARP inhibitors, Yang et al. performed a drug screen and discovered that BET inhibitors, a type of epigenetic regulators, act synergistically with PARP inhibitors. The authors found that BET inhibitors suppress homologous recombination, inducing the functional defect that sensitizes tumors to PARP inhibitors. The authors demonstrated the effectiveness of this combination approach in models of breast and ovarian cancer. They also provided genetic data showing that BET inhibitors may be able to target many other tumor types, suggesting that this combination treatment may have broad applicability.