Proteomics uncover EPHA2 as a potential novel therapeutic target in colorectal cancer cell lines with acquired cetuximab resistance.

Background: In metastatic colorectal cancer (mCRC), acquired resistance against anti-EGFR targeted monoclonal antibodies, such as cetuximab (CET), was shown to be frequently caused by activating alterations in the RAS genes KRAS or NRAS. To this day, no efficient follow-up treatment option has emerged to treat mCRC in such a setting of resistance.

Methods: To uncover potential targets for second-line targeted therapies, we used mass-spectrometric proteomics to shed light on kinome reprogramming in an established cellular model of acquired, KRAS-associated CET resistance.