Analysis of the role of RAS Family Mutations in Metastatic Colorectal Cancer (mCRC): Current Treatment Practice

A major challenge in metastatic colorectal cancer (mCRC) is the identification of specific biomarkers that are likely to predict which patients will benefit from a specific treatment. To this date, a number of studies have shown that a tumour's mutational profile influences treatment outcome in patients with mCRC and should, therefore, be used to guide treatment decision. For more than 5 years now, we know that patients with tumours harbouring mutations in exon 2, codons 12 and 13 of the KRAS oncogene gain no benefit from the administration of anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (moAbs), Cetuximab and Panitumumab. It has just recently being elucidated that KRAS mutations outside codons 12 and 13 and mutations in the NRAS gene confer resistance to Cetuximab and Panitumumab, as well. Thus, since June 2013, the analysis of exons 2, 3 and 4 of KRAS and NRAS has been incorporated in daily clinical practice to improve patients’ selection for anti-EGFR moAbs treatment. Nevertheless, even if patients’ outcome under anti-EGFR moAbs therapy is improved with better selection based on Ras mutational status, more research is needed in this field; the matter is far from being resolved, since there are still a minority of wt RAS patients who do not respond upfront to such a treatment.