The emerging HER2 landscape in colorectal cancer: the key to unveil the future treatment algorithm?
Jacopo Venturini, Giulia Massaro, Daniele Lavacchi, Daniele Rossini, Serena Pillozzi, Enrico Caliman, Elisa Pellegrini, Lorenzo Antonuzzo
Abstract
Colorectal cancer (CRC) represents a global health threat, standing as the second leading cause of cancer-related death worldwide. Targeted therapies brought new hope for the metastatic stage, which historically bore a very poor prognosis. Human epidermal growth receptor 2 (HER2) overexpression concerns about 5 % of the metastatic CRC (mCRC) patients, including both gene amplifications and point mutations. Albeit its controversial prognostic role, preclinical and clinical data indicate HER2 as a negative predictive biomarker of response to anti-EGFR therapies. Tissue and plasma-based NGS testing, could permit a precise identification of this resistance mechanism both at baseline and during treatment, thus guiding decision-making. Furthermore, promising results come from completed and ongoing randomized trials, testing HER2 as an actionable target. In this review, we discuss the available evidence on HER2 targeting in advanced CRC, analyzing its possible future role in the treatment algorithm. • HER2 overexpression stands as a negative predictive biomarker of response to anti-EGFR therapies in mCRC. • Completed and ongoing randomized trials tested ERBB2 as an actionable target, showing promising results. • HER2 mutation play a very complex role, possibly acting as resistance mechanism to anti-EGFR and anti-HER2 agents. • In the era of tailored treatments, NGS techniques on tissue and plasmatic samples constitute the cornerstone for the future of clinical decision-making.