Abstract
The introduction of monoclonal antibodies targeting the epidermal growth factor receptor (EGFR) has represented a milestone in the management of metastatic colorectal cancer (mCRC). Cetuximab significantly improves outcomes in patients with RAS wild-type tumors, yet only about one third derive durable benefit. This discrepancy underscores the biological heterogeneity of EGFR signaling and the urgent need for biomarkers capable of predicting therapeutic response beyond RAS status.