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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 | 2021-01-27T05:13:13Z | - |
dc.date.available | 2021-01-27T14:22:38Z | - |
dc.date.issued | 2020-11-20 | - |
dc.identifier.citation | Molecular Cancer. 2020 Nov 20;19(1):161 | ko_KR |
dc.identifier.issn | 1476-4598 | - |
dc.identifier.uri | https://hdl.handle.net/10371/171711 | - |
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 CD24low/CD44high 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. | ko_KR |
dc.description.sponsorship | This research was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI12C1852, HA17C0053, HR20C0021), the National Research Foundation (NRF) funded by the Korean government (MSIT) (grant number:
2018R1A2B6005347, 2018R1D1A1B07045416, 2019M3E5D1A01068998), and was supported by a Korea University Guro Hospital grant (grant number: O1904001), and the Brain Korea (BK) 21 Plus Program. | ko_KR |
dc.language.iso | en | ko_KR |
dc.publisher | BMC | ko_KR |
dc.subject | C-terminal HSP90 inhibitor | - |
dc.subject | NCT-547 | - |
dc.subject | HER2-positive breast cancer | - |
dc.subject | Cancer stem cells | - |
dc.subject | Trastuzumab resistance | - |
dc.subject | p95HER2, HER2 | - |
dc.title | A novel HSP90 inhibitor targeting the C-terminal domain attenuates trastuzumab resistance in HER2-positive breast cancer | ko_KR |
dc.type | Article | ko_KR |
dc.contributor.AlternativeAuthor | 박정민 | - |
dc.contributor.AlternativeAuthor | 김윤재 | - |
dc.contributor.AlternativeAuthor | 박소은 | - |
dc.contributor.AlternativeAuthor | 박민수 | - |
dc.contributor.AlternativeAuthor | 남기범 | - |
dc.contributor.AlternativeAuthor | 박현주 | - |
dc.contributor.AlternativeAuthor | 이지우 | - |
dc.contributor.AlternativeAuthor | 김지영 | - |
dc.contributor.AlternativeAuthor | 서재홍 | - |
dc.identifier.doi | 10.1186/s12943-020-01283-6 | - |
dc.citation.journaltitle | Molecular Cancer | ko_KR |
dc.language.rfc3066 | en | - |
dc.rights.holder | The Author(s) | - |
dc.date.updated | 2020-11-22T04:30:45Z | - |
dc.citation.number | 1 | ko_KR |
dc.citation.startpage | 161 | ko_KR |
dc.citation.volume | 19 | ko_KR |
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