Are Fragment C Gamma Receptor (FCGR) Germline Polymorphisms Predictive Biomarkers in Metastatic Colorectal Cancer

The treatment of metastatic colorectal cancer has undergone significant improvements over the last decade with the introduction of molecularly targeted monoclonal antibodies (mAbs). Among these, cetuximab, a chimeric IgG1 antibody directed against the extracellular domain of EGFR, has demonstrated a survival benefit for KRAS wild type (WT) tumors. Even though KRAS genotyping has significantly refined patient selection allowing an increase in tumor radiological response from 25% of the whole metastatic colorectal cancer (MCRC) population to 45% of the KRAS-WT subset, still for a significant proportion of patients anti-EGFR mAbs will be ineffective, thus resulting in unnecessary toxicity and cost. Polymorphisms of Fragment C gamma receptor (FCGR) gene have the potential for being used as predictive biomarkers of cetuximab activity since part of this drug’s tumoricidal effect is immune-mediated via FcγR-triggered ADCC (antibody-dependent cellular cytotoxicity). The aim of the present review is to summarize available data on the predictive/prognostic value of FCGR polymorphisms for cetuximab-treated MCRC patients and to discuss possible future directions in this area of research.