Clinical relevance of KRAS mutations in codon 13: Where are we?

• Personalized medicine in colorectal cancer has made significant improvement in patients survival after metastasis development.
• Publications demonstrate that KRAS mutations in codon 12 and 13 have different effects regarding to anti-EGFR treatment.
• Studies made on the biological role of KRAS mutation in codon 13 support its putative prognostic and putative value.
• KRAS mutations in codon 13 confers worse prognosis and outcome than those in codon 12.
• Cetuximab provides advantage to KRAS G13D patients, mostly due to a higher disease control and PFS.

Recent advances in molecular diagnosis and the trend towards personalized medicine have made colorectal cancer one of the tumors where therapies have significantly improved patient survival after metastasis development. KRAS mutations in codon 12 and 13 are recognized biomarkers that are analyzed in clinic previously for anti-EGFR therapies administration. Since originally mutations in both codons were considered as a predictor of lack of response to cetuximab or panitumumab, the European Medicines Agency and the US Food and Drug Administration suggested that patients harboring any of those mutations should be excluded from the treatment. However, subsequent retrospective analysis has shown that mutations in codon 12 and codon 13 of KRAS gene could be different in their biological characteristics and as a result could confer variable effects in patients. In addition and increasing and sometimes contradictory number of solutions have been published demonstrating that patients with mutations in codon 13 could have worse outcome but could obtain a significant clinical benefit from anti-EGFR therapies. Here, we review and update the latest data on the biological role leading to a predictive outcome and benefit from anti-EGFR antibodies in patients with specific KRAS mutations in codon 13.