دورية أكاديمية
Combination of Type I and Type II MET Tyrosine Kinase Inhibitors as Therapeutic Approach to Prevent Resistance
| العنوان: | Combination of Type I and Type II MET Tyrosine Kinase Inhibitors as Therapeutic Approach to Prevent Resistance |
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| المساهمون: | Magda Bahcall, Cloud P Paweletz, Yanan Kuang, Luke J Taus, Taebo Sim, Nam Doo Kim, Kshiti H Dholakia, Christie J Lau, Prafulla C Gokhale, Pratik R Chopade, Fangxin Hong, Zihan Wei, Jens Köhler, Paul T Kirschmeier, Jiannan Guo, Sujuan Guo, Stephen Wang, Pasi A Jänne, Sim, Taebo |
| بيانات النشر: | American Association for Cancer Research |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Animals, Drug Resistance, Neoplasm / drug effects, Female, High-Throughput Nucleotide Sequencing / methods, Humans, Mice, Molecular Docking Simulation / methods, Protein Kinase Inhibitors / pharmacology, Protein Kinase Inhibitors / therapeutic use |
| الوصف: | MET-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. ; restriction |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1535-7163 1538-8514 |
| العلاقة: | MOLECULAR CANCER THERAPEUTICS; J02254; OAK-2022-02281; https://ir.ymlib.yonsei.ac.kr/handle/22282913/188552Test; https://aacrjournals.org/mct/article/21/2/322/678522/Combination-of-Type-I-and-Type-II-MET-TyrosineTest; T202201478; MOLECULAR CANCER THERAPEUTICS, Vol.21(2) : 322-335, 2022-02 |
| DOI: | 10.1158/1535-7163.MCT-21-0344 |
| الإتاحة: | https://doi.org/10.1158/1535-7163.MCT-21-0344Test https://ir.ymlib.yonsei.ac.kr/handle/22282913/188552Test https://aacrjournals.org/mct/article/21/2/322/678522/Combination-of-Type-I-and-Type-II-MET-TyrosineTest |
| حقوق: | CC BY-NC-ND 2.0 KR |
| رقم الانضمام: | edsbas.98E31984 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 15357163 15388514 |
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| DOI: | 10.1158/1535-7163.MCT-21-0344 |