HER2 in Colorectal Cancer: The Long and Winding Road From Negative Predictive Factor to Positive Actionable Target

Human epidermal growth factor receptor 2 (HER2) is a well-known oncogenic driver in different tumors and an approved therapeutic target in breast and gastroesophageal cancer. In metastatic colorectal cancer, only 3% to 5% of patients present with HER2 alterations: somatic mutations and amplifications. HER2 was first assessed as a biomarker of resistance to anti-EGFR therapy; however, in more recent years, its role as a potential actionable target has emerged. In this article, we discuss the predictive and prognostic value of HER2 in metastatic colorectal cancer, its emerging role as an actionable therapeutic target, and its possible future developments.