posted on 2016-08-29, 00:00authored byAmanda Stone, Kymberly Harrington, Mark Frakes, Kory Blank, Supriya Rajanna, Ichwaku Rastogi, Neelu Puri
EGFR and c-Met are receptor tyrosine kinases that are implicated in tumor development and progression in
several types of cancer. Both EGFR and c-Met, which are known to be overexpressed and mutated in cancer, share
common signaling pathways, including the PI3K/ Akt and MAPK pathways. Small molecule tyrosine kinase inhibitors
and monoclonal antibodies that work against EGFR and c-Met are at the forefront of cancer therapy, but their
individual efficacies are limited due to the development of drug resistance. In recent pre-clinical studies, we
observed that combination therapy using mTOR and Wnt inhibitors with EGFR or c-Met tyrosine kinase inhibitors
resulted in overcoming drug resistance. Our studies also indicated that EGFR and c-Met tyrosine kinase inhibitor
resistance may be due to activation of alternative signaling pathways. The development of additional combinatorial
therapies is underway, and various combinations of inhibitors have shown promising results in clinical trials. Future
studies in this direction could be the basis for development of new cancer therapeutics, utilizing EGFR and c-Met
inhibitors, which could greatly improve patient prognosis.