Your browser doesn't support javascript.
loading
MET Signaling Pathways, Resistance Mechanisms, and Opportunities for Target Therapies.
Rivas, Solange; Marín, Arnaldo; Samtani, Suraj; González-Feliú, Evelin; Armisén, Ricardo.
Afiliación
  • Rivas S; Centro de Genética y Genómica, Instituto de Ciencias e Innovación en Medicina, Facultad de Medicina Clínica Alemana, Universidad del Desarrollo, Santiago 7550000, Chile.
  • Marín A; Departamento de Oncología Básico Clínica, Facultad de Medicina, Universidad de Chile, Santiago 8380000, Chile.
  • Samtani S; Departamento de Oncología Médica, Clínica Las Condes, Santiago 7550000, Chile.
  • González-Feliú E; Hospital Félix Bulnes, Santiago 9080000, Chile.
  • Armisén R; Centro de Genética y Genómica, Instituto de Ciencias e Innovación en Medicina, Facultad de Medicina Clínica Alemana, Universidad del Desarrollo, Santiago 7550000, Chile.
Int J Mol Sci ; 23(22)2022 Nov 11.
Article en En | MEDLINE | ID: mdl-36430388
ABSTRACT
The MET gene, known as MET proto-oncogene receptor tyrosine kinase, was first identified to induce tumor cell migration, invasion, and proliferation/survival through canonical RAS-CDC42-PAK-Rho kinase, RAS-MAPK, PI3K-AKT-mTOR, and ß-catenin signaling pathways, and its driver mutations, such as MET gene amplification (METamp) and the exon 14 skipping alterations (METex14), activate cell transformation, cancer progression, and worse patient prognosis, principally in lung cancer through the overactivation of their own oncogenic and MET parallel signaling pathways. Because of this, MET driver alterations have become of interest in lung adenocarcinomas since the FDA approval of target therapies for METamp and METex14 in 2020. However, after using MET target therapies, tumor cells develop adaptative changes, favoring tumor resistance to drugs, the main current challenge to precision medicine. Here, we review a link between the resistance mechanism and MET signaling pathways, which is not only limited to MET. The resistance impacts MET parallel tyrosine kinase receptors and signals shared hubs. Therefore, this information could be relevant in the patient's mutational profile evaluation before the first target therapy prescription and follow-up to reduce the risk of drug resistance. However, to develop a resistance mechanism to a MET inhibitor, patients must have access to the drugs. For instance, none of the FDA approved MET inhibitors are registered as such in Chile and other developing countries. Constant cross-feeding between basic and clinical research will thus be required to meet future challenges imposed by the acquired resistance to targeted therapies.
Asunto(s)
Palabras clave

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fosfatidilinositol 3-Quinasas / Neoplasias Pulmonares Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Int J Mol Sci Año: 2022 Tipo del documento: Article País de afiliación: Chile

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fosfatidilinositol 3-Quinasas / Neoplasias Pulmonares Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Int J Mol Sci Año: 2022 Tipo del documento: Article País de afiliación: Chile
...