V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog also known as KRAS is a protein which in humans is encoded by the KRAS gene. KRAS has been extensively studied in a wide array of human malignancies, including mCRC. Mutant KRAS can be detected in approximately 30-50% of colorectal cancers. The Ras-Raf-MAPK pathway lies just downstream of EGFR.

The presence of the V600E mutation in the BRAF gene is associated with poor prognosis and non response to anti-EGFR therapy in advanced stage colorectal cancer patients. Studies show that colorectal cancer patients with wild-type KRAS failed to respond when treated with either cetuximab or panitumumab and experienced a shorter progression-free survival and overall survival, when the BRAF mutation was present, compared to patients with wild-type BRAF tumors.1