Publications
Detailed Information
AZD9291, an Irreversible EGFR TKI, Overcomes T790M-Mediated Resistance to EGFR Inhibitors in Lung Cancer
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Cross, Darren A. E. | - |
dc.contributor.author | Ashton, Susan E. | - |
dc.contributor.author | Ghiorghiu, Serban | - |
dc.contributor.author | Eberlein, Cath | - |
dc.contributor.author | Nebhan, Caroline A. | - |
dc.contributor.author | Spitzler, Paula J. | - |
dc.contributor.author | Orme, Jonathon P. | - |
dc.contributor.author | Finlay, M. Raymond V. | - |
dc.contributor.author | Ward, Richard A. | - |
dc.contributor.author | Mellor, Martine J. | - |
dc.contributor.author | Hughes, Gareth | - |
dc.contributor.author | Rahi, Amar | - |
dc.contributor.author | Jacobs, Vivien N. | - |
dc.contributor.author | Brewer, Monica Red | - |
dc.contributor.author | Ichihara, Eiki | - |
dc.contributor.author | Sun, Jing | - |
dc.contributor.author | Jin, Hailing | - |
dc.contributor.author | Ballard, Peter | - |
dc.contributor.author | Al-Kadhimi, Katherine | - |
dc.contributor.author | Rowlinson, Rachel | - |
dc.contributor.author | Klinowska, Teresa | - |
dc.contributor.author | Richmond, Graham H. P. | - |
dc.contributor.author | Cantarini, Mireille | - |
dc.contributor.author | Kim, Dong-Wan | - |
dc.contributor.author | Ranson, Malcolm R. | - |
dc.contributor.author | Pao, William | - |
dc.date.accessioned | 2020-04-27T11:24:56Z | - |
dc.date.available | 2020-04-27T11:24:56Z | - |
dc.date.created | 2020-02-19 | - |
dc.date.issued | 2014-09 | - |
dc.identifier.citation | Cancer Discovery, Vol.4 No.9, pp.1046-1061 | - |
dc.identifier.issn | 2159-8274 | - |
dc.identifier.other | 91739 | - |
dc.identifier.uri | https://hdl.handle.net/10371/165412 | - |
dc.description.abstract | First-generation EGFR tyrosine kinase inhibitors (EGFR TKI) provide significant clinical benefit in patients with advanced EGFR-mutant (EGFRm(+)) non-small cell lung cancer (NSCLC). Patients ultimately develop disease progression, often driven by acquisition of a second T790M EGFR TKI resistance mutation. AZD9291 is a novel oral, potent, and selective third-generation irreversible inhibitor of both EGFRm(+) sensitizing and T790M resistance mutants that spares wild-type EGFR. This mono-anilino-pyrimidine compound is structurally distinct from other third-generation EGFR TKIs and offers a pharmacologically differentiated profile from earlier generation EGFR TKIs. Preclinically, the drug potently inhibits signaling pathways and cellular growth in both EGFRm(+) and EGFRm(+)/T790M(+) mutant cell lines in vitro, with lower activity against wild-type EGFR lines, translating into profound and sustained tumor regression in EGFR-mutant tumor xenograft and transgenic models. The treatment of 2 patients with advanced EGFRm(+) T790M(+) NSCLC is described as proof of principle. SIGNIFICANCE: We report the development of a novel structurally distinct third-generation EGFR TKI, AZD9291, that irreversibly and selectively targets both sensitizing and resistant T790M(+) mutant EGFR while harboring less activity toward wild-type EGFR. AZD9291 is showing promising responses in a phase I trial even at the first-dose level, with first published clinical proof-of-principle validation being presented. (C) 2014 AACR. | - |
dc.language | 영어 | - |
dc.publisher | American Association for Cancer Research Inc. | - |
dc.title | AZD9291, an Irreversible EGFR TKI, Overcomes T790M-Mediated Resistance to EGFR Inhibitors in Lung Cancer | - |
dc.type | Article | - |
dc.contributor.AlternativeAuthor | 김동완 | - |
dc.identifier.doi | 10.1158/2159-8290.CD-14-0337 | - |
dc.citation.journaltitle | Cancer Discovery | - |
dc.identifier.wosid | 000343121400027 | - |
dc.identifier.scopusid | 2-s2.0-84904898065 | - |
dc.citation.endpage | 1061 | - |
dc.citation.number | 9 | - |
dc.citation.startpage | 1046 | - |
dc.citation.volume | 4 | - |
dc.identifier.sci | 000343121400027 | - |
dc.description.isOpenAccess | Y | - |
dc.contributor.affiliatedAuthor | Kim, Dong-Wan | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.subject.keywordPlus | GROWTH-FACTOR RECEPTOR | - |
dc.subject.keywordPlus | TYROSINE KINASE INHIBITOR | - |
dc.subject.keywordPlus | ACQUIRED-RESISTANCE | - |
dc.subject.keywordPlus | T790M MUTATIONS | - |
dc.subject.keywordPlus | 1ST-LINE TREATMENT | - |
dc.subject.keywordPlus | GENE-MUTATIONS | - |
dc.subject.keywordPlus | SOLID TUMORS | - |
dc.subject.keywordPlus | OPEN-LABEL | - |
dc.subject.keywordPlus | PHASE-III | - |
dc.subject.keywordPlus | GEFITINIB | - |
- Appears in Collections:
- Files in This Item:
- There are no files associated with this item.
Item View & Download Count
Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.