Journal of Genetic Syndromes & Gene Therapy
Open Access

Abstract

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

Formica V, Cereda V, Nardecchia A, Morelli C, Lucchetti J and Roselli M

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.