Optimization of the Development of Old and New EGFR and MAP Kinase Inhibitors for Colorectal Cancer

The epidermal growth factor receptor (EGFR) and its downstream signaling pathways are crucially important in the biology of colorectal cancer (CRC). In the past few years, EGFR kinase and its major downstream effector, the RAS/RAF/MAPK/ERK pathway, have been attractive targets for development of new therapy for treatment of metastatic CRC (mCRC). Cetuximab and panitumumab, two monoclonal antibodies (mAbs) against the EGFR, are the first targeted agents approved as personalized medicine for treatment of mCRC. Recently, inhibition of MEK1/2 has been seen as a promising approach for blocking MAPK-mediated proliferation signals. Several compounds with highly selective inhibitory effects on MEK1/2 have been developed and have entered clinical trials. New therapeutic agents have also been used to optimize personalized treatment of mCRC. In this context we discuss recent advances in research on EGFR and MAPK inhibitors.