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Preclinical Study of a Biparatopic METxMET Antibody-Drug Conjugate, REGN5093-M114, Overcomes MET-driven Acquired Resistance to EGFR TKIs in EGFR-mutant NSCLC
DC Field | Value | Language |
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dc.contributor.author | 임선민 | - |
dc.contributor.author | 조병철 | - |
dc.contributor.author | 김재환 | - |
dc.contributor.author | 박영준 | - |
dc.contributor.author | 허성구 | - |
dc.contributor.author | 홍민희 | - |
dc.contributor.author | 윤미란 | - |
dc.contributor.author | 유미라 | - |
dc.date.accessioned | 2023-07-12T02:41:06Z | - |
dc.date.available | 2023-07-12T02:41:06Z | - |
dc.date.issued | 2023-01 | - |
dc.identifier.issn | 1078-0432 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/195372 | - |
dc.description.abstract | Purpose: MET amplification is a frequent mechanism of resistance to EGFR tyrosine kinase inhibitors (TKI) in patients with EGFR-mutated non-small cell lung cancer (NSCLC), and combined treatment with EGFR TKIs and MET TKIs has been explored as a strategy to overcome resistance. However, durable response is invariably limited by the emergence of acquired resistance. Here, we investigated the preclinical activity of REGN5093-M114, a novel antibody-drug conjugate targeting MET in MET-driven patient-derived models. Experimental Design: Patient-derived organoids, patient-derived cells, or ATCC cell lines were used to investigate the in vitro/in vivo activity of REGN5093-M114. Results: REGN5093-M114 exhibited significant antitumor efficacy compared with METTKI or unconjugated METxMET biparatopic antibody (REGN5093). Regardless of MET gene copy number, MET-overexpressed TKI-naive EGFR-mutant NSCLC cells responded to REGN5093-M114 treatment. Cell surface MET expression had the most predictive power in determining the efficacy of REGN5093-M114. REGN5093-M114 potently reduced tumor growth of EGFR-mutant NSCLC with PTEN loss or MET Y1230C mutation after progression on prior osimertinib and savolitinib treatment. Conclusions: Altogether, REGN5093-M114 is a promising candidate to overcome the challenges facing functional MET pathway blockade., | - |
dc.description.statementOfResponsibility | restriction | - |
dc.language | English | - |
dc.publisher | American Association for Cancer Research | - |
dc.relation.isPartOf | CLINICAL CANCER RESEARCH | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.subject.MESH | Carcinoma, Non-Small-Cell Lung* / drug therapy | - |
dc.subject.MESH | Carcinoma, Non-Small-Cell Lung* / genetics | - |
dc.subject.MESH | Carcinoma, Non-Small-Cell Lung* / pathology | - |
dc.subject.MESH | Cell Line, Tumor | - |
dc.subject.MESH | Drug Resistance, Neoplasm / genetics | - |
dc.subject.MESH | ErbB Receptors | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Immunoconjugates* / therapeutic use | - |
dc.subject.MESH | Lung Neoplasms* / drug therapy | - |
dc.subject.MESH | Lung Neoplasms* / genetics | - |
dc.subject.MESH | Lung Neoplasms* / pathology | - |
dc.subject.MESH | Mutation | - |
dc.subject.MESH | Protein Kinase Inhibitors / pharmacology | - |
dc.subject.MESH | Protein Kinase Inhibitors / therapeutic use | - |
dc.subject.MESH | Proto-Oncogene Proteins c-met | - |
dc.title | Preclinical Study of a Biparatopic METxMET Antibody-Drug Conjugate, REGN5093-M114, Overcomes MET-driven Acquired Resistance to EGFR TKIs in EGFR-mutant NSCLC | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Internal Medicine (내과학교실) | - |
dc.contributor.googleauthor | Seung Yeon Oh | - |
dc.contributor.googleauthor | You Won Lee | - |
dc.contributor.googleauthor | Eun Ji Lee | - |
dc.contributor.googleauthor | Jae Hwan Kim | - |
dc.contributor.googleauthor | YoungJoon Park | - |
dc.contributor.googleauthor | Seong Gu Heo | - |
dc.contributor.googleauthor | Mi Ra Yu | - |
dc.contributor.googleauthor | Min Hee Hong | - |
dc.contributor.googleauthor | John DaSilva | - |
dc.contributor.googleauthor | Christopher Daly | - |
dc.contributor.googleauthor | Byoung Chul Cho | - |
dc.contributor.googleauthor | Sun Min Lim | - |
dc.contributor.googleauthor | Mi Ran Yun | - |
dc.identifier.doi | 10.1158/1078-0432.CCR-22-2180 | - |
dc.contributor.localId | A03369 | - |
dc.contributor.localId | A03822 | - |
dc.relation.journalcode | J00564 | - |
dc.identifier.pmid | 36269795 | - |
dc.identifier.url | https://aacrjournals.org/clincancerres/article/29/1/221/711969 | - |
dc.contributor.alternativeName | Lim, Sun Min | - |
dc.contributor.affiliatedAuthor | 임선민 | - |
dc.contributor.affiliatedAuthor | 조병철 | - |
dc.citation.volume | 29 | - |
dc.citation.number | 1 | - |
dc.citation.startPage | 221 | - |
dc.citation.endPage | 232 | - |
dc.identifier.bibliographicCitation | CLINICAL CANCER RESEARCH, Vol.29(1) : 221-232, 2023-01 | - |
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