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RESEARCH PRODUCT
The role of cMET in non-small cell lung cancer resistant to EGFR-Inhibitors: Did we really find the target?
Karen ZwaenepoelChristian RolfoEdgardo S. SantosAntonio RussoNele Van Der SteenSantini DanieleGiuseppe BronteFrancesco PassigliaGiovanni TesorierePatrick PauwelsIgnacio Gil-bazoFederico CappuzzoLuis E. Raezsubject
Lung NeoplasmscMETcMET; cMET-Inhibitors; EGFR-TKIs resistance; HGF; NSCLC; Targeted therapies; Molecular Medicine; Pharmacology; Drug Discovery3003 Pharmaceutical Science; Clinical BiochemistryClinical BiochemistryAntineoplastic AgentsBiologyPharmacologyNSCLCReceptor tyrosine kinaseTargeted therapiesCarcinoma Non-Small-Cell LungDrug DiscoverymedicineHumansEpidermal growth factor receptorHGFLung cancerProtein Kinase InhibitorsEGFR inhibitorsEGFR-TKIs resistancePharmacologyClinical Trials as TopicPharmacology. TherapyDrug Discovery3003 Pharmaceutical ScienceAntibodies MonoclonalProto-Oncogene Proteins c-metmedicine.diseaseMolecular medicinerespiratory tract diseasesErbB ReceptorsDrug Resistance NeoplasmProto-Oncogene Proteins c-metbiology.proteinCancer researchMolecular MedicineDrug Therapy CombinationHepatocyte growth factorcMET-InhibitorTargeted therapiecMET-InhibitorsTyrosine kinasemedicine.drugdescription
Abstract: The advent of the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) represented the most important innovation in NSCLC treatment over the last years. However, despite a great initial activity, secondary mutations in the same target, or different alterations in other molecular pathways, inevitably occur, leading to the emergence of acquired resistance, in median within the first year of treatment. In this scenario, the mesenchymal-epidermal transition (cMET) tyrosine kinase receptor and its natural ligand, the hepatocyte growth factor (HGF), seem to play an important role. Indeed either the overexpression or the amplification of cMET, as well as the overexpression of the HGF, have been reported in a substantial subgroup of NSCLC patients resistant to EGFR-TKIs. Several cMET-inhibitors have been developed as potential therapeutic candidates, and are currently under investigation in clinical trials. These compounds include both monoclonal antibodies and TKIs, and most of them have been investigated as dual combinations including an anti-EGFR TKI, to improve the efficacy of the available treatments, and ultimately overcome acquired resistance to EGFR-inhibitors.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2014-01-01 |