Approximately 16% of patients with metastatic colorectal cancer (mCRC), have developed the EGFR S492R mutation following treatment with cetuximab.[8] Mutations of various other residues of EGFR (e.g., V441, I462, S464, G465, K467, K489, I491) have also been associated with the ability of the receptor to confer clinical resistance to cetuximab.[7, 9] Efforts to circumvent the cetuximab resistance resulting from EGFR ECD mutations have been primarily focused on developing new anti‐EGFR mAbs or utilizing combinatorial strategies. Here, EGFR is linked to metastatic colorectal cancer.