From a therapeutic point of view, HER-3-targeted therapies based on the use of monoclonal antibodies, such as patritumab [17] and seribantumab [16], or bispecific monoclonal antibodies against EGFR/HER-3, such as duligotuzumab [18], did not have a great success in terms of clinical benefit in metastatic colorectal cancer patients in clinical trials. This evidence concerns the gene ERBB3 and metastatic colorectal cancer.