RIVAS VERA, SOLANGE VERÓNICASOLANGE VERÓNICARIVAS VERAArnaldo MarínSuraj SamtaniEvelin González-FeliúARMISEN YAÑEZ, RICARDO AMADORICARDO AMADOARMISEN YAÑEZ2023-01-122023-01-122022Rivas, S., Marín, A., Samtani, S., González-Feliú, E., & Armisén, R. (2022). Met signaling pathways, resistance mechanisms, and opportunities for target therapies. International Journal of Molecular Sciences, 23(22), 13898. https://doi.org/10.3390/ijms232213898http://hdl.handle.net/11447/6672https://investigadores.udd.cl/handle/123456789/532310.3390/ijms2322138982-s2.0-85142790823WOS:000887388100001<jats:p>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 β-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.</jats:p>actionable mutationsdriver mutationsnsclcprecision medicineresistance mutationstarget therapiesexonshumanslung neoplasmsphosphatidylinositol 3-kinasesproto-oncogene proteins c-metsignal transductionbeta catenincabozantinibcapmatinibchloroplast dnacrizotinibepidermal growth factor receptor 3focal adhesion kinasegefitinibmammalian target of rapamycinmessenger rnamitogen activated protein kinaseosimertinibphosphatidylinositol 3 kinaseprotein kinase bprotein tyrosine kinase inhibitorras proteinsavolitinibscatter factor receptortepotinibtrametinibtyrosine kinase receptorwnt proteinphosphatidylinositol 3 kinasescatter factor receptorcancer resistancecancer survivalcell invasioncell motilitycell proliferationclinical researchclinical trial (topic)developing countrydna determinationdrug approvalexon skippingfeedingfollow upfood and drug administrationgene amplificationgene dosagegene mutationgenetic resistancehumanmalignant neoplasmmelanomamolecularly targeted therapymutationnon small cell lung cancerpersonalized medicinephase 2 clinical trial (topic)phase 3 clinical trial (topic)prescriptionreviewrisk assessmentrisk factorsignal transductionsmall cell lung cancertreatment indicationexonlung tumormetabolismpathologysignal transductionResource Types::text::journal::journal article