Issues

Harbinski and colleagues performed a high-throughput screen of the human secretome to identify proteins capable of rescuing growth of receptor tyrosine kinase (RTK)–addicted cells following RTK inhibition and observed numerous potential ligand-mediated resistance mechanisms. Multiple human epidermal growth factor (HER) and fibroblast growth factor (FGF) ligands could rescue growth of hepatocyte growth factor (HGF) receptor (MET)–addicted cancer cells following MET inhibition, and FGFR-addicted cell lines treated with FGFR inhibitors could be rescued by HER ligands or HGF. Combination therapy modalities targeting the broad compensatory relationship between MET, FGFR, and HER ligands may thus have improved clinical efficacy. For details, please see the article by Harbinski and colleagues on page 948.