Predictive factors of response to targeted therapies: the example of colorectal cancer

Abstract

EGF receptor (EGFR), the VEGF and its receptors represent currently the most promising therapeutic targets in colorectal cancer. Strategies of EGFR targeting have been numerous with mainly monoclonal antibodies specifically binding the extracellular domain of the EGFR and enzymatic inhibitors of the intracellular part of the receptors with tyrosine kinase activity. These two latter therapeutic tools have been under active clinical development. The clinical application currently the most successful is the association of the anti-EGFR monoclonal antibody cetuximab with irinotecan in metastatic colorectal cancer. Recent clinical data point on panitumumab as another good candidate. The therapeutic classes used to antagonize the EGFR were applied as well for VEGF targeting. Encouraging clinical results came from the association between an anti-VEGF antibody, bevacizumab, with 5FU-folinic acid combination. Reliable predictive tools are needed to apply these treatments for potentially sensitive tumors only. This review underlines the lack of clinically-validated tools so as to provide a firm answer to this crucial question.