Abstract 376: Increased HGF is associated with resistance to VEGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC)

Emergence of therapeutic resistance to angiogenesis inhibitors, the mechanisms of which are poorly understood, remains a major obstacle in treatment of NSCLC patients. Previously we reported that mechanisms governing resistance to anti-angiogenic therapy may involve both tumor and stromal cells in the tumor microenvironment. In this study we investigated potential mechanisms of resistance to the multi-tyrosine kinase inhibitors cediranib (AZD2171, Recentin ® ) and vandetanib (ZD6474, Zactima ® ) using NSCLC xenografts treated either for 2 weeks (sensitive tumors) or until resistance occurred. Quantification of TUNEL + staining using laser scanning cytometry (LSC) showed increased apoptosis in H1975 xenografts sensitive to cediranib (p ® ). Differentially modulated genes were selected based on a p Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 376.