1. Cell-autonomous mechanisms of resistance to targeted therapies involving the HGF/MET axis.
Cell-autonomous mechanisms of resistance to targeted therapies involving the HGF/MET axis. A, MET gene amplification results in overexpression of the receptor and HER3 transphosphorylation in NSCLC cells in which EGFR is inhibited by specific TKIs. B, chromosome 7 duplication results in increased copy number of both HGF and MET and, thus, in increased MET-dependent signal transduction. This results in resistance to trastuzumab in breast cancer cells. C, upon EGFR inhibition, a substantial increase in MET expression is responsible for sustained prosurvival AKT signaling, leading to resistance to EGFR TKIs in glioblastoma. D, MET gene amplification, causing receptor overexpression and activation of downstream pathways, induces resistance to cetuximab and panitumumab in colorectal cancer.
Simona Corso, and Silvia Giordano Cancer Discovery 2013;3:
©2013 by American Association for Cancer Research