miRNAs as modulators of EGFR therapy in colorectal cancer

Abstract

Drug resistance is a serious impediment to the treatment of cancer. The use of anti-epidermal growth factor receptor (EGFR) monoclonal antibody therapies in patients with metastatic colorectal cancer is guided by the presence of activating point mutations in KRAS and NRAS genes in the primary tumour. However, RAS wild-type status is still not sufficient to guarantee response to cetuximab and panitumumab, with response rates limited to 70% for combinations with multidrug chemotherapy. Therefore, additional mechanisms contributing to resistance are currently under investigation, and include genetic alterations and epigenetic mechanisms of resistance. In this regard, deregulation of miRNA expression profiles holds potential to unveil resistance and fuel the development of miRNA-based strategies to overcome EGFR-directed therapy limitations. We discuss current understanding of miRNA impact as modulators of EGFR therapy in patients with metastatic colorectal cancer and the future challenge of miRNAs in circulation as powerful non-invasive tools to monitor anti-EGFR therapy response and predict resistance.