Henceforth, the further expansion of the knowledge between the connection of HER2 and CRC led to the identification of HER2-activating mutations also causing resistance to EGFR monoclonal antibodies and provided new intervention possibilities using dual anti-HER2 targeted therapy for the management of patients suffering from HER2-mutated KRAS-wt CRC [56, 57]. This evidence concerns the gene ERBB2 and colorectal carcinoma.