Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.
Cancer Discov. 2013 May;3(5):491-3. doi: 10.1158/2159-8290.CD-13-0128.
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.
在一组人类肺癌细胞系的小分子抑制剂筛选中，出人意料地发现表达致癌 KRAS 的细胞对胰岛素样生长因子 1 受体 (IGF1R) 抑制敏感。联合 IGF1R 和 MAP-ERK 激酶阻断导致人类非小细胞肺癌 (NSCLC) 细胞系和 2 种致癌 KRAS 驱动的肺癌小鼠模型中的细胞活力有显著影响。这种效应的机制基础似乎是表达致癌 KRAS 的细胞中 IGF1R 介导的 AKT 激活的基线活性增加。因此，这些研究为治疗 KRAS 驱动的 NSCLC 提供了一种新的方法，这是现有方法治疗特别困难的患者亚群。
