Targeting the MET-Signaling Pathway in Non-Small–Cell Lung Cancer: Evidence to Date
| Autor: | Jean-Baptiste Assié, Christos Chouaid, O. Bylicki, Nicolas Paleiron |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Mutation Lung business.industry Mechanism (biology) Met amplification medicine.disease medicine.disease_cause respiratory tract diseases 3. Good health 03 medical and health sciences 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis medicine Cancer research Pharmacology (medical) Signal transduction Lung cancer Receptor business Carcinogenesis |
| Zdroj: | OncoTargets and Therapy. 13:5691-5706 |
| ISSN: | 1178-6930 |
| DOI: | 10.2147/ott.s219959 |
| Popis: | The c-MET proto-oncogene (MET) plays an important role in lung oncogenesis, affecting cancer-cell survival, growth and invasiveness. The MET receptor in non-small-cell lung cancer (NSCLC) is a potential therapeutic target. The development of high-output next-generation sequencing techniques has enabled better identification of anomalies in the MET pathway, like the MET exon-14 (METex14) mutation. Moreover, analyses of epidermal growth factor-receptor (EGFR) and mechanisms of resistance to tyrosine-kinase inhibitors (TKIs) demonstrated the importance of MET amplification as an escape mechanism in patients with TKI-treated EGFR-mutated NSCLCs. This review summarizes the laboratory findings on MET and its anomalies, trial results on METex14 alterations and MET amplification in non-EGFR mutated NSCLCs, and acquired resistance to TKI in EGFR-mutated NSCLCs. The outcomes of the first trials with anti-MET agents on non-selected NSCLC patients or those selected for MET overexpression were disappointing. Two situations seem the most promising today for the use of anti-MET agents to treat these patients: tumors harboring METex14 and those EGFR-sensitive mutation mutated under TKI-EGFR with a MET-amplification mechanism of resistance or EGFR-resistance mutation. |
| Databáze: | OpenAIRE |
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