and inhibition as treatment strategies in V600E metastatic colorectal cancer.

INTRODUCTION

driver mutations are found in up to 15% of patients with colorectal cancer (CRC) and lead to constitutive activation of kinase and sustained pathway signaling. mutations define a sub-population characterized by a poor prognosis and dismal median survival. Following successful outcomes with inhibition in mutant metastatic melanoma, this approach was evaluated in metastatic colorectal cancer (mCRC). The development and combination of targeted therapies against multiple signaling pathways has proved particularly successful, with improved survival and response rates.

AREAS COVERED

This review addresses the development of therapeutic strategies with inhibitors targeting MAPK/ERK and signaling in V600E mutated mCRC, focusing on encorafenib, binimetinib and cetuximab. A pharmacological and clinical review of these drugs and the therapeutic approaches behind their optimization are presented.

EXPERT OPINION

Exploiting knowledge of the mechanisms of resistance to inhibitors has been crucial to developing effective therapeutic strategies in mutant mCRC. The BEACON trial is a successful example of this approach, using encorafenib and cetuximab with or without binimetinib in patients with previously treated V600E mutant mCRC, showing an impressive improvement in clinical outcomes and tolerable toxicity compared with chemotherapy, establishing a new standard of care in this setting.