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Combination of Type I and Type II MET Tyrosine Kinase Inhibitors as Therapeutic Approach to Prevent Resistance

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dc.contributor.author심태보-
dc.date.accessioned2022-05-09T17:24:42Z-
dc.date.available2022-05-09T17:24:42Z-
dc.date.issued2022-02-
dc.identifier.issn1535-7163-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/188552-
dc.description.abstractMET-targeted therapies are clinically effective in MET-amplified and MET exon 14 deletion mutant (METex14) non-small cell lung cancers (NSCLCs), but their efficacy is limited by the development of drug resistance. Structurally distinct MET tyrosine kinase inhibitors (TKIs) (type I/II) have been developed or are under clinical evaluation, which may overcome MET-mediated drug resistance mechanisms. In this study, we assess secondary MET mutations likely to emerge in response to treatment with single-agent or combinations of type I/type II MET TKIs using TPR-MET transformed Ba/F3 cell mutagenesis assays. We found that these inhibitors gave rise to distinct secondary MET mutant profiles. However, a combination of type I/II TKI inhibitors (capmatinib and merestinib) yielded no resistant clones in vitro The combination of capmatinib/merestinib was evaluated in vivo and led to a significant reduction in tumor outgrowth compared with either MET inhibitor alone. Our findings demonstrate in vitro and in vivo that a simultaneous treatment with a type I and type II MET TKI may be a clinically viable approach to delay and/or diminish the emergence of on target MET-mediated drug-resistance mutations.-
dc.description.statementOfResponsibilityrestriction-
dc.languageEnglish-
dc.publisherAmerican Association for Cancer Research-
dc.relation.isPartOfMOLECULAR CANCER THERAPEUTICS-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.subject.MESHAnimals-
dc.subject.MESHDrug Resistance, Neoplasm / drug effects*-
dc.subject.MESHFemale-
dc.subject.MESHHigh-Throughput Nucleotide Sequencing / methods*-
dc.subject.MESHHumans-
dc.subject.MESHMice-
dc.subject.MESHMolecular Docking Simulation / methods*-
dc.subject.MESHProtein Kinase Inhibitors / pharmacology-
dc.subject.MESHProtein Kinase Inhibitors / therapeutic use*-
dc.titleCombination of Type I and Type II MET Tyrosine Kinase Inhibitors as Therapeutic Approach to Prevent Resistance-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentBioMedical Science Institute (의생명과학부)-
dc.contributor.googleauthorMagda Bahcall-
dc.contributor.googleauthorCloud P Paweletz-
dc.contributor.googleauthorYanan Kuang-
dc.contributor.googleauthorLuke J Taus-
dc.contributor.googleauthorTaebo Sim-
dc.contributor.googleauthorNam Doo Kim-
dc.contributor.googleauthorKshiti H Dholakia-
dc.contributor.googleauthorChristie J Lau-
dc.contributor.googleauthorPrafulla C Gokhale-
dc.contributor.googleauthorPratik R Chopade-
dc.contributor.googleauthorFangxin Hong-
dc.contributor.googleauthorZihan Wei-
dc.contributor.googleauthorJens Köhler-
dc.contributor.googleauthorPaul T Kirschmeier-
dc.contributor.googleauthorJiannan Guo-
dc.contributor.googleauthorSujuan Guo-
dc.contributor.googleauthorStephen Wang-
dc.contributor.googleauthorPasi A Jänne-
dc.identifier.doi10.1158/1535-7163.MCT-21-0344-
dc.contributor.localIdA05926-
dc.relation.journalcodeJ02254-
dc.identifier.eissn1538-8514-
dc.identifier.pmid34789563-
dc.identifier.urlhttps://aacrjournals.org/mct/article/21/2/322/678522/Combination-of-Type-I-and-Type-II-MET-Tyrosine-
dc.contributor.alternativeNameSim, Taebo-
dc.contributor.affiliatedAuthor심태보-
dc.citation.volume21-
dc.citation.number2-
dc.citation.startPage322-
dc.citation.endPage335-
dc.identifier.bibliographicCitationMOLECULAR CANCER THERAPEUTICS, Vol.21(2) : 322-335, 2022-02-
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers

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