An allosteric inhibitor against the therapy-resistant mutant forms of EGFR in non-small cell lung cancer
DC Field | Value | Language |
---|---|---|
dc.contributor.author | To, Ciric | - |
dc.contributor.author | Beyett, Tyler S. | - |
dc.contributor.author | Jang, Jaebong | - |
dc.contributor.author | Feng, William W. | - |
dc.contributor.author | Bahcall, Magda | - |
dc.contributor.author | Haikala, Heidi M. | - |
dc.contributor.author | Shin, Bo H. | - |
dc.contributor.author | Heppner, David E. | - |
dc.contributor.author | Rana, Jaimin K. | - |
dc.contributor.author | Leeper, Brittaney A. | - |
dc.contributor.author | Soroko, Kara M. | - |
dc.contributor.author | Poitras, Michael J. | - |
dc.contributor.author | Gokhale, Prafulla C. | - |
dc.contributor.author | Kobayashi, Yoshihisa | - |
dc.contributor.author | Wahid, Kamal | - |
dc.contributor.author | Kurppa, Kari J. | - |
dc.contributor.author | Gero, Thomas W. | - |
dc.contributor.author | Cameron, Michael D. | - |
dc.contributor.author | Ogino, Atsuko | - |
dc.contributor.author | Mushajiang, Mierzhati | - |
dc.contributor.author | Xu, Chunxiao | - |
dc.contributor.author | Zhang, Yanxi | - |
dc.contributor.author | Scott, David A. | - |
dc.contributor.author | Eck, Michael J. | - |
dc.contributor.author | Gray, Nathanael S. | - |
dc.contributor.author | Janne, Pasi A. | - |
dc.date.accessioned | 2022-06-10T17:40:40Z | - |
dc.date.available | 2022-06-10T17:40:40Z | - |
dc.date.created | 2022-06-09 | - |
dc.date.issued | 2022-04 | - |
dc.identifier.issn | 2662-1347 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/141877 | - |
dc.description.abstract | Janne and colleagues discover and characterize an allosteric EGFR inhibitor with efficacy against therapy-resistant mutations and show preclinical efficacy as monotherapy and in combination in patient-derived xenograft models. Epidermal growth factor receptor (EGFR) therapy using small-molecule tyrosine kinase inhibitors (TKIs) is initially efficacious in patients with EGFR-mutant lung cancer, although drug resistance eventually develops. Allosteric EGFR inhibitors, which bind to a different EGFR site than existing ATP-competitive EGFR TKIs, have been developed as a strategy to overcome therapy-resistant EGFR mutations. Here we identify and characterize JBJ-09-063, a mutant-selective allosteric EGFR inhibitor that is effective across EGFR TKI-sensitive and resistant models, including those with EGFR T790M and C797S mutations. We further uncover that EGFR homo- or heterodimerization with other ERBB family members, as well as the EGFR L747S mutation, confers resistance to JBJ-09-063, but not to ATP-competitive EGFR TKIs. Overall, our studies highlight the potential clinical utility of JBJ-09-063 as a single agent or in combination with EGFR TKIs to define more effective strategies to treat EGFR-mutant lung cancer. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | NATURE PORTFOLIO | - |
dc.subject | 1ST-LINE TREATMENT | - |
dc.subject | OPEN-LABEL | - |
dc.subject | MUTATION | - |
dc.subject | OSIMERTINIB | - |
dc.subject | GEFITINIB | - |
dc.subject | EFFICACY | - |
dc.subject | AFATINIB | - |
dc.subject | CHEMOTHERAPY | - |
dc.subject | MULTICENTER | - |
dc.subject | ERLOTINIB | - |
dc.title | An allosteric inhibitor against the therapy-resistant mutant forms of EGFR in non-small cell lung cancer | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Jang, Jaebong | - |
dc.identifier.doi | 10.1038/s43018-022-00351-8 | - |
dc.identifier.scopusid | 2-s2.0-85128059021 | - |
dc.identifier.wosid | 000782543600003 | - |
dc.identifier.bibliographicCitation | NATURE CANCER, v.3, no.4, pp.402 - + | - |
dc.relation.isPartOf | NATURE CANCER | - |
dc.citation.title | NATURE CANCER | - |
dc.citation.volume | 3 | - |
dc.citation.number | 4 | - |
dc.citation.startPage | 402 | - |
dc.citation.endPage | + | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Oncology | - |
dc.relation.journalWebOfScienceCategory | Oncology | - |
dc.subject.keywordPlus | 1ST-LINE TREATMENT | - |
dc.subject.keywordPlus | OPEN-LABEL | - |
dc.subject.keywordPlus | MUTATION | - |
dc.subject.keywordPlus | OSIMERTINIB | - |
dc.subject.keywordPlus | GEFITINIB | - |
dc.subject.keywordPlus | EFFICACY | - |
dc.subject.keywordPlus | AFATINIB | - |
dc.subject.keywordPlus | CHEMOTHERAPY | - |
dc.subject.keywordPlus | MULTICENTER | - |
dc.subject.keywordPlus | ERLOTINIB | - |
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
(02841) 서울특별시 성북구 안암로 14502-3290-1114
COPYRIGHT © 2021 Korea University. All Rights Reserved.
Certain data included herein are derived from the © Web of Science of Clarivate Analytics. All rights reserved.
You may not copy or re-distribute this material in whole or in part without the prior written consent of Clarivate Analytics.