Indeed, using in vitro analysis of EGFR overexpressing CRC parental (DiFi) and drug-resistant variant (DiFi62) cells, we have previously shown enhanced activation of both HER2 and HER3 as a novel mechanism of drug resistance against anti-EGFR mAbs ICR62 and cetuximab and highlighted the therapeutic benefits of using pan-HER inhibitors following the development of acquired resistance to EGFR antibody-based therapy [106]. This evidence concerns the gene EGFR and colorectal carcinoma.