Research ArticleCancer

Development of combination therapies to maximize the impact of KRAS-G12C inhibitors in lung cancer

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Science Translational Medicine  18 Sep 2019:
Vol. 11, Issue 510, eaaw7999
DOI: 10.1126/scitranslmed.aaw7999

Cutting off tumors’ escape routes

Cancer-driving mutations in the KRAS oncogene are common in many cancer types, including lung cancer. The combination of inhibitors for the kinases MEK and IGF1R is effective in KRAS-mutant lung cancer, but some cancer cells can still survive this treatment. Molina-Arcas et al. used an shRNA screening approach to identify another category of drugs that can be added to the therapeutic regimen to enhance its effectiveness. The authors then substituted an inhibitor of mutant KRAS to replace the MEK inhibitor in the combination to decrease treatment toxicity. The resulting triple-drug combination showed promising results in mouse models, with improved efficacy and tolerability.

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