KDR Amplification Is Associated with VEGF-Induced Activation of the mTOR and Invasion Pathways but does not Predict Clinical Benefit to the VEGFR TKI Vandetanib.

ABSTRACT:

Purpose

VEGF pathway inhibitors have been investigated as therapeutic agents in the treatment of non-small cell lung cancer (NSCLC) because of its central role in angiogenesis. These agents have improved survival in patients with advanced NSCLC, but the effects have been modest. Although VEGFR2/KDRis typically localized to the vasculature, amplification ofKDRhas reported to occur in 9% to 30% of the DNA from different lung cancers. We investigated the signaling pathways activated downstream ofKDRand whetherKDRamplification is associated with benefit in patients with NSCLC treated with the VEGFR inhibitor vandetanib.

Methods

NSCLC cell lines with or withoutKDRamplification were studied for the effects of VEGFR tyrosine kinase inhibitors (TKI) on cell viability and migration.

SUBMITTER: Nilsson MB 

PROVIDER: S-EPMC4834253 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature