HER2-targeted therapy: an emerging strategy in advanced colorectal cancer

Introduction: Colorectal cancer (CRC) is one of the most common malignant tumors; it is a focus of research globally, but the identification of clinically actionable oncogenic drivers remains elusive. Human epidermal growth factor receptor 2 (HER2) activation is present in approximately 5% of CRC and has acquired resistance to epidermal growth factor receptor (EGFR)-targeted therapy. Early clinical trials suggest an emerging role for personalized HER2-targeted therapy in a subset of metastatic CRC. Areas covered: This manuscript reviews the relevance of HER2 activation in CRC and its potential role as a target for therapy. A literature search was conducted in June 2018 of MEDLINE and EMBASE databases for published preclinical and clinical studies; abstracts of international cancer meetings (AACR, ASCO, and ESMO) were also reviewed. Expert opinion: HER2 is activated in a small but relevant proportion of CRC patients (particularly left-side, RAS wild-type, anti-EGFR resistant tumors). Dual HER2 blockade with monoclonal antibodies (mAbs) (trastuzumab and pertuzumab) or the combination of mAbs with tyrosine kinase inhibitors (trastuzumab and lapatinib) induces durable tumor responses in about one-third of HER2-positive CRC refractory to standard systemic therapy. Although immature, these results are remarkable and anticipate an expanding role for HER2 as a therapeutic target in CRC.