title: Two is better than one: combining IGF1R and MEK blockade as a promising novel treatment strategy against KRAS-mutant lung cancer.
abstract: 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.
authors: Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.
authors: Ron
authors: R
authors: Chen
authors: E Alejandro
authors: EA
authors: Sweet-Cordero
mesh_terms: D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D018631:ras Proteins / Q000235:genetics*
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D019869:Phosphatidylinositol 3-Kinases; D017526:Receptor, IGF Type 1; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins
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