KRAS mutation detection: a new look at an old gene.

The introduction of small-molecule drugs and humanized monoclonal antibodies as novel therapies that target specific receptors and proteins in specific signal-transduction pathways has renewed interest in genes that had previously been identified as being involved in the tumorigenic process. The first of these genes was the ERBB2 [v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian)] oncogene (also known as HER2), a member of the epidermal growth factor receptor (EGFR) family, which is amplified in human breast cancer. Diagnostic interests in this gene were never peaked until this receptor became the target of Herceptin, the first monoclonal antibody therapy against a cellular receptor. Similarly, EGFR has become the target of both monoclonal antibody therapies that target the binding domain and small-molecule drugs that inhibit its tyrosine kinase activity. KRAS (v-Kiras2 Kirsten rat sarcoma viral oncogene homolog) is a known oncogene that typically functions in the EGFR pathway. Although mutations in this oncogene are known to be associated with various types of human cancer, only recently has it become an attractive biomarker for the clinical laboratory and healthcare provider as a mechanism to determine therapeutic options. KRAS mutation detection has become part of the standard workup of patients with colorectal cancer, and those tumors that harbor a KRAS mutation have been shown to be nonresponsive to anti-EGFR therapies. The implementation of KRAS mutation testing in a clinical laboratory environment is surveyed below among 4 pathologists and a medical oncologist from 4 leading medical institutions in the US. Is KRAS mutation testing performed routinely at your institution? If so, for which clinical indications? If not, what are the barriers that are affecting implementation?