A novel HSP90 inhibitor targeting the C-terminal domain attenuates trastuzumab resistance in HER2-positive breast cancer
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Park, Jung Min | - |
dc.contributor.author | Kim, Yoon-Jae | - |
dc.contributor.author | Park, Soeun | - |
dc.contributor.author | Park, Minsu | - |
dc.contributor.author | Farrand, Lee | - |
dc.contributor.author | Nguyen, Cong-Truong | - |
dc.contributor.author | Ann, Jihyae | - |
dc.contributor.author | Nam, Gibeom | - |
dc.contributor.author | Park, Hyun-Ju | - |
dc.contributor.author | Lee, Jeewoo | - |
dc.contributor.author | Kim, Ji Young | - |
dc.contributor.author | Seo, Jae Hong | - |
dc.date.accessioned | 2021-08-30T05:21:40Z | - |
dc.date.available | 2021-08-30T05:21:40Z | - |
dc.date.created | 2021-06-18 | - |
dc.date.issued | 2020-12-20 | - |
dc.identifier.issn | 1476-4598 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/50783 | - |
dc.description.abstract | Trastuzumab resistance in HER2-positive breast cancer is associated with a poorer prognosis. HSP90 is thought to play a major role in such resistance, but N-terminal inhibitors of this target have had little success. We sought to investigate the utility of NCT-547, a novel, rationally-designed C-terminal HSP90 inhibitor in the context of overcoming trastuzumab resistance. NCT-547 treatment significantly induced apoptosis without triggering the heat shock response (HSR), accompanied by caspase-3/- 7 activation in both trastuzumab-sensitive and -resistant cells. NCT-547 effectively promoted the degradation of full-length HER2 and truncated p95HER2, while also attenuating hetero-dimerization of HER2 family members. The impairment of cancer stem-like traits was observed with reductions in ALDH1 activity, the CD24(low)/CD44(high) subpopulation, and mammosphere formation in vitro and in vivo. NCT-547 was an effective inhibitor of tumor growth and angiogenesis, and no toxic outcomes were found in initial hepatic and renal analysis. Our findings suggest that NCT-547 may have applications in addressing trastuzumab resistance in HER2-positive breast cancer. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | BMC | - |
dc.title | A novel HSP90 inhibitor targeting the C-terminal domain attenuates trastuzumab resistance in HER2-positive breast cancer | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Seo, Jae Hong | - |
dc.identifier.doi | 10.1186/s12943-020-01283-6 | - |
dc.identifier.scopusid | 2-s2.0-85096325840 | - |
dc.identifier.wosid | 000591128900001 | - |
dc.identifier.bibliographicCitation | MOLECULAR CANCER, v.19, no.1 | - |
dc.relation.isPartOf | MOLECULAR CANCER | - |
dc.citation.title | MOLECULAR CANCER | - |
dc.citation.volume | 19 | - |
dc.citation.number | 1 | - |
dc.type.rims | ART | - |
dc.type.docType | Letter | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalResearchArea | Oncology | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Oncology | - |
dc.subject.keywordAuthor | C-terminal HSP90 inhibitor | - |
dc.subject.keywordAuthor | NCT-547 | - |
dc.subject.keywordAuthor | HER2-positive breast cancer | - |
dc.subject.keywordAuthor | Cancer stem cells | - |
dc.subject.keywordAuthor | Trastuzumab resistance | - |
dc.subject.keywordAuthor | p95HER2 | - |
dc.subject.keywordAuthor | HER2 | - |
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
145 Anam-ro, Seongbuk-gu, Seoul, 02841, Korea+82-2-3290-2963
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.