Two is better than one: combining IGF1R and MEK blockade as a promising novel treatment strategy against KRAS-mutant lung cancer.

A small-molecule inhibitor screen on a panel of human lung cancer cell lines has uncovered an unexpected sensitivity of cells expressing oncogenic KRAS toward insulin-like growth factor 1 receptor (IGF1R) inhibition. Combining IGF1R and MAP-ERK kinase blockade led to significant effects on viability in human non-small cell lung cancer (NSCLC) cell lines and in 2 mouse models of oncogenic KRAS-driven lung cancer. The mechanistic basis for this effect seems to be an increased baseline activation of IGF1R-mediated activation of AKT in cells that express oncogenic KRAS. The studies thus point to a novel approach for treatment of KRAS-driven NSCLC, a particularly difficult subset of patients to treat with existing approaches.