Beyond KRAS Status and Response to Anti-EGFR Therapy in Metastatic Colorectal Cancer

Abstract

In patients with metastatic colorectal cancer, overall survival has improved over the last decade mainly due to the use of effective targeted therapies such as anti-EGFR. However, survival improvement is linked to proper selection of patients expected to benefit from these treatments. KRAS codons 12 and 13 mutation status was the first validated molecular biomarker for anti-EGFR antibodies. Today, rare KRAS alterations and NRAS mutations were implemented, defining the ‘RAS’ status as the new validated marker of response to anti-EGFR antibodies. Moreover, other biomarkers are under investigation to screen for other targets and help with patients selection. Here, we reviewed these promising biomarkers: mutations in the RAS–MAPK and PI3K–AKT pathways genes, MET activation, HER/ErbB receptors activation (EGFR, HER2 and HER3), EGFR ligands, antibody-dependent cell-mediated cytotoxicity) and miRNAs. Further data are needed to define their impact for the treatment of patients with metastatic colorectal cancer.

Keywords::

• biomarkers
• cancer
• cetuximab
• colorectal
• KRAS
• panitumumab

Financial & competing interests disclosure

P Laurent-Puig is a consultant/advisory board member of Amgen and Merck Serono. G Perkins received a grant from Merck Serono. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

P Laurent-Puig is a consultant/advisory board member of Amgen and Merck Serono. G Perkins received a grant from Merck Serono. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.