Exon 14 Deleted MET Receptor as a New Biomarker and Target in Cancers
| Autor: | David Tulasne, Alexis B. Cortot, Marie Wislez, Zoulika Kherrouche, C. Descarpentries, Alessandro Furlan, Simon Baldacci |
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| Přispěvatelé: | Mécanismes de la Tumorigénèse et Thérapies Ciblées - UMR 8161 (M3T), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), This work was supported by the CNRS, the Institut Pasteur de Lille, and INSERM, and by grants from the 'Ligue contre le Cancer, comité Nord,' the 'Association pour la Recherche sur le Cancer,' the 'Institut National du Cancer,' the 'Cancéropôle Nord-Ouest,' and the 'Site de Recherche Intégrée sur le Cancer, SIRIC ONCOLille.', FURLAN, Alessandro, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP) |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cancer Research neoplasms medicine.disease_cause protein-tyrosine kinase inhibitor exons Receptor tyrosine kinase Exon 0302 clinical medicine MESH: Molecular Targeted Therapy Medicine MESH: Animals Epidermal growth factor receptor Molecular Targeted Therapy Receptor Mutation biology MESH: Gene Expression Regulation Neoplastic Protein-Tyrosine Kinases Proto-Oncogene Proteins c-met 3. Good health Gene Expression Regulation Neoplastic MESH: Neoplasms/drug therapy Oncology 030220 oncology & carcinogenesis Tyrosine kinase MESH: Mutation MESH: Biomarkers Tumor/genetics [SDV.CAN]Life Sciences [q-bio]/Cancer MESH: Protein-Tyrosine Kinases/antagonists & inhibitors 03 medical and health sciences [SDV.CAN] Life Sciences [q-bio]/Cancer MESH: Neoplasms/genetics Biomarkers Tumor Animals Humans cancer Protein Kinase Inhibitors MESH: Humans business.industry Cancer MESH: Exons medicine.disease MESH: Protein Kinase Inhibitors/therapeutic use MESH: Proto-Oncogene Proteins c-met/genetics MESH: Neoplasms/diagnosis 030104 developmental biology Protein kinase domain biology.protein Cancer research mutation business |
| Zdroj: | JNCI: Journal of the National Cancer Institute JNCI: Journal of the National Cancer Institute, 2017, 109 (5), pp.djw262. ⟨10.1093/jnci/djw262⟩ JNCI: Journal of the National Cancer Institute, Oxford University Press (OUP), 2017, 109 (5), pp.djw262. ⟨10.1093/jnci/djw262⟩ |
| ISSN: | 0027-8874 1460-2105 |
| DOI: | 10.1093/jnci/djw262⟩ |
| Popis: | International audience; Inhibitors of the receptor tyrosine kinase (RTK) MET have been ineffective at treating cancer, possibly because of lack of knowledge that would allow selection of tumors likely to respond to this treatment. In contrast, specific epidermal growth factor receptor (EGFR) inhibitors have been used successfully against lung tumors displaying activating mutations in the kinase domain of EGFR. Recent publications describe a set of mutations causing MET exon 14 skipping, and importantly, several case reports describe objective responses to MET-targeting tyrosine kinase inhibitors in patients with such mutations. These observations suggest a novel therapeutic strategy for fighting cancer, especially in the lung. Exon 14 encodes the MET juxtamembrane domain targeted by mechanisms that negatively regulate receptor stability and activity. In this review, we describe the molecular mechanisms leading first to exon 14 skipping and then to activation of the MET receptor and how this process differs from that triggered by classical RTK-activating mutations in the kinase domain. We detail the clinical characteristics of patients carrying these mutations and the sensitivity of their tumors to MET inhibitors. Lastly, we discuss future challenges related to MET mutations in cancers, including patient screening and anticipating resistance to MET inhibitors. |
| Databáze: | OpenAIRE |
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