Chapter 3 - MM-151 overcomes acquired resistance to cetuximab and panitumumab in colorectal cancers harboring EGFR extracellular domain mutations

Abstract

Cetuximab and panitumumab are used to treat RAS wild-type colorectal cancer (CRC) through the target of EGFR (epidermal growth factor receptor), but after EGFR signaling pathway blockade, approximately 20% of CRCs develop EGFR extracellular domain (ECD) mutations. Impaired antibody binding is associated with clinical recurrence. The oligoclonal antibody MM-151 developed by researchers binds to several regions of the EGFR ECD to address resistance and recurrence caused by mutations in the EGFR ECD. MM-151 blocked EGFR and inhibited cell growth in a preclinical model, including tumors with EGFR mutations. MM-151 treatment can prevent EGFR ECD mutations in CRC patients who have already developed resistance to EGFR blockade. These data provide a new strategy to treat patients who have developed resistance to anti-EGFR monoclonal antibodies due to EGFR ECD mutations.