HER2 as a Predictive Biomarker and Treatment Target in Colorectal Cancer

Abstract

The prognosis of metastatic colorectal cancer (mCRC) is poor. Cetuximab and panitumumab, 2 anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs), improve the overall survival of patients with RAS wild-type mCRC. However, not all patients with RAS wild-type mCRC will respond to anti-EGFR mAbs. Several retrospective trials suggest that human epidermal growth factor receptor 2 (HER2) amplification could be a predictive biomarker of resistance to anti-EGFR mAbs in patients with metastatic RAS and RAF wild-type mCRC. Dual HER2 inhibition with trastuzumab plus lapatinib or pertuzumab has shown promising preliminary anti-tumoral efficacy in RAS wild-type mCRC. Although these findings need to be confirmed in randomized trials, the data strongly support that HER2 is an actionable gene in CRC and provide the scientific rationale to test HER2 status on a routine basis in this disease. In this review, we discuss the predictive value of HER2 activation in CRC as well as its potential role as a treatment target.

Keywords: Drug resistance; Epidermal growth factor receptor; Gene amplification; Human epidermal growth factor receptor 2; Targeted therapy.