title: 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.
authors: Institut National de la Santé et de la Recherche Médicale (INSERM), Unité Mixte de Recherche (UMR)-S1147, Personalized Medicine, Pharmacogenomics, Therapeutic Optimization, University Paris Descartes, 45 rue des Saints Pères, Paris 75006, France.
authors: Geraldine
authors: G
authors: Perkins
authors: Camilla
authors: C
authors: Pilati
authors: Helene
authors: H
authors: Blons
authors: Pierre
authors: P
authors: Laurent-Puig
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000276:immunology; D006801:Humans; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000235:genetics*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D019869:Phosphatidylinositol 3-Kinases; C512478:EGFR protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins
keywords: KRAS; biomarkers; cancer; cetuximab; colorectal; panitumumab