KRAS and metastatic colorectal cancer: KRAS mutations in the exon 2 are reportedly predictive of resistance to anti-EGFR mAb therapy, and a retrospective analysis of RAS mutations in specimens from a randomized trial of combination chemotherapy for metastatic colorectal cancer (the PRIME trial) indicated that, similar to KRAS exon 2, mutations in KRAS exons 3 and 4 and NRAS exons 2, 3, and 4 were negative predictive factors to panitumumab [28].