KRAS, BRAF, PIK3CA, and PTEN mutations: implications for targeted therapies in metastatic colorectal cancer

The discovery of mutant KRAS as a predictor of resistance to epidermal growth-factor receptor (EGFR) monoclonal antibodies brought a major change in the treatment of metastatic colorectal cancer. This seminal finding also highlighted our sparse knowledge about key signalling pathways in colorectal tumours. Drugs that inhibit oncogenic alterations such as phospho-MAP2K (also called MEK), phospho-AKT, and mutant B-RAF seem promising as single treatment or when given with EGFR inhibitors. However, our understanding of the precise role these potential drug targets have in colorectal tumours, and the oncogenic dependence that tumours might have on these components, has not progressed at the same rate. As a result, patient selection and prediction of treatment effects remain problematic. We review the role of mutations in genes other than KRAS on the efficacy of anti-EGFR therapy, and discuss strategies to target these oncogenic alterations alone or in combination with receptor tyrosine-kinase inhibition.

Indexed on Europe PMC as PubMed record 21163703 (DOI 10.1016/s1470-2045(10)70209-6). Its title names PIK3CA and its text names Colorectal cancer; PubMed types it as a review (Research Support, Non-U.S. Gov't, Review). It was matched automatically to the idea "Get biomarker-directed aspirin after colorectal surgery into labels and guidelines" and no figure has been checked by an editor.