Molecular predictors of response to EGFR antibodies in colorectal cancer

Abstract

Cetuximab and panitumumab, antibodies against the epidermal growth factor receptor (EGFR), have been shown to be effective in treating irinotecan-resistant and chemorefractory metastatic colorectal cancer, respectively. However, these costly and potentially toxic treatments are effective in only a small proportion of patients. It is important to identify markers that can better define which patients will benefit from these treatments. The major potential molecular predictive markers of response to cetuximab or panitumumab are involved more or less directly in the EGF signaling pathway. Among them, KRAS mutations, EGFR gene copy number, and, more recently, expression of the PTEN protein and the epiregulin and amphiregulin genes appear to be the most relevant; these must be evaluated in future clinical trials before they are incorporated into the therapeutic strategy for colorectal cancer.