Development of novel targeted therapy for lung cancer with activating Ras mutation

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There are still no effective targeted therapies for patients with K-ras activating mutations which is a cause of intrinsic resistance to EGFR-TKI. Here, we assessed therapeutic effect of β-phenylthyl isothiocynate (PEITC) on lung cancer cellswith K-ras activating mutations through production of reactive oxygen species (ROS).Treatment with PEITC reduced cell viability and induced apoptosis in K-ras mutant lung cancer cells. In a xenograft model, PEITC dramatically reduced tumor growth with less toxicity. Moreover, normal human fibloblasts and K-ras wild lung cancer cells weresignificantly less sensitive to PEITC. Our findings suggest that PEITC can selectively kill lung cancer cells with K-ras activating mutations.