Research ArticleCancer

Rational combination therapy with PARP and MEK inhibitors capitalizes on therapeutic liabilities in RAS mutant cancers

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Science Translational Medicine  31 May 2017:
Vol. 9, Issue 392, eaal5148
DOI: 10.1126/scitranslmed.aal5148

No escape for KRAS mutant tumors

Alterations in one of the RAS proteins, such as KRAS, are among the most common oncogenic mutations and also among the most difficult to treat. RAS mutant tumors are usually resistant to PARP inhibitors, one of the newest classes of anticancer therapeutics, and many other chemotherapy types. However, Sun et al. have discovered that inhibition of MEK or ERK (proteins in the RAS pathway) can reverse PARP inhibitor resistance in KRAS mutant tumors. MEK and PARP inhibitors are clinically approved drugs that provide a readily translatable therapeutic combination, and the authors have demonstrated its effectiveness in mouse models of aggressive tumors such as ovarian and pancreatic cancer.

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