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.
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- Authors
- Perkins, G., Pilati, C., Blons, H., & Laurent-Puig, P.
- Affiliations
- 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
- Inserm (FR)
- ORCID
- Pilati, Camilla
- Venue
- Pharmacogenomics
- Publisher
- Informa UK Limited
- Published
- 2014-05
- Volume
- 15
- Issue
- 7
- Pages
- 1043-1052
- ISSN
- 1462-2416 (ISSN-L)
- 1744-8042
- OpenAlex
- W2000591164
- Cited by
- 22
- References
- 12
- Citations by year
- 2025: 3 · 2023: 3 · 2021: 1 · 2019: 3 · 2018: 3 · 2017: 1 · 2016: 5 · 2015: 2 · 2014: 1
- FWCI
- 0.34
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pharmacogenomics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Merck Serono
- Topics
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Keywords
- metastatic colorectal cancer, anti-EGFR therapy, KRAS mutation, NRAS mutation, RAS status, predictive biomarkers, RAS/MAPK pathway, PI3K/Akt signaling, MET activation, HER2, HER3, EGFR ligands, antibody-dependent cellular cytotoxicity, microRNA, patient selection
- MeSH terms
- Humans, Mutation, Proto-Oncogene Proteins, Biomarkers, Tumor, Colorectal Neoplasms, Proto-Oncogene Proteins p21(ras), ras Proteins, Phosphatidylinositol 3-Kinases, Antibodies, Monoclonal, Humanized, ErbB Receptors
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