KRAS mutations and sensitivity to anti-EGFR monoclonal antibodies in metastatic colorectal carcinoma: an open issue.

Background: Cetuximab and panitumumab, mAbs targeting EGFR, are registered for metastatic colorectal carcinoma (mCRC) patients whose tumors express EGFR as determined by immunohistochemistry. However, this method is not predictive of treatment efficacy. KRAS, the human homolog of the Kirsten rat sarcoma-2 virus oncogene, encodes a small G-protein that functions downstream of EGFR-induced signalling. Objective/Methods: To examine KRAS mutations as predictive factors of response to anti-EGFR mAbs using recently published data. Results/conclusions: Several retrospective studies show that efficacy of these mAbs is confined to patients with wild type KRAS and genotyping of tumors should be considered before treatment. The absence of KRAS mutations does not guarantee an improved likelihood of response to cetuximab and panitumumab. Investigation of other genetic and epigenetic biomarkers will be useful to further refine the responder population. Prospective studies to test the efficacy of combined therapies simultaneously targeting EGFR and the RAS/RAF/MAPK signalling pathways for mCRC are warranted.