A critical review of the role of Fc gamma receptor polymorphisms in the response to monoclonal antibodies in cancer.

Antibody-dependent cellular cytotoxicity (ADCC) is a major mechanism of action of therapeutic monoclonal antibodies (mAbs) such as cetuximab, rituximab and trastuzumab. Fc gamma receptors (FcgR) on human white blood cells are an integral part of the ADCC pathway. Differential response to therapeutic mAbs has been reported to correlate with specific polymorphisms in two of these genes: FCGR2A (H131R) and FCGR3A (V158F). These polymorphisms are associated with differential affinity of the receptors for mAbs. This review critically examines the current evidence for genotyping the corresponding single nucleotide polymorphisms (SNPs) to predict response to mAbs in patients with cancer.