KRAS mutational testing in the selection of patients for EGFR-targeted therapies

The small-molecule epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors and the anti-EGFR monoclonal antibodies have proven activity ill and colorectal adenocarcinomas, respectively, but only a small fraction of patients exhibit significant responses. The observation that only a minority of patients respond to EGFR-targeted therapies, in combination with their toxicity and high costs. has driven the search for molecular markers predictive of response. The main focus of the present review is the recent discovery that Mutations in the KRAS oncogene constitute a negative predictive marker in this clinical setting, namely that their presence call be used to predict which patients are unlikely to benefit front treatment with EGFR-directed therapy. (C) 2008 Elsevier Inc. All rights reserved.