A novel HSP90 inhibitor SL-145 suppresses metastatic triple-negative breast cancer without triggering the heat shock responseopen access
- Authors
- Kim, Ji Young; Cho, Tae-Min; Park, Jung Min; Park, Soeun; Park, Minsu; Dal Nam, Kee; Ko, Dongmi; Seo, Juyeon; Kim, Seongjae; Jung, Eunsun; Farrand, Lee; Nguyen, Cong-Truong; Hoang, Van-Hai; La, Minh Thanh; Ann, Jihyae; Nam, Gibeom; Park, Hyun-Ju; Lee, Jeewoo; Kim, Yoon-Jae; Seo, Jae Hong
- Issue Date
- 3-6월-2022
- Publisher
- SPRINGERNATURE
- Citation
- ONCOGENE, v.41, no.23, pp.3289 - 3297
- Indexed
- SCIE
SCOPUS
- Journal Title
- ONCOGENE
- Volume
- 41
- Number
- 23
- Start Page
- 3289
- End Page
- 3297
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/142234
- DOI
- 10.1038/s41388-022-02269-y
- ISSN
- 0950-9232
- Abstract
- Despite recent advances, there remains a significant unmet need for the development of new targeted therapies for triple-negative breast cancer (TNBC). Although the heat shock protein HSP90 is a promising target, previous inhibitors have had issues during development including undesirable induction of the heat shock response (HSR) and off-target effects leading to toxicity. SL-145 is a novel, rationally-designed C-terminal HSP90 inhibitor that induces apoptosis in TNBC cells via the suppression of oncogenic AKT, MEK/ERK, and JAK2/STAT3 signaling and does not trigger the HSR, in contrast to other inhibitors. In an orthotopic allograft model incorporating breast cancer stem cell-enriched TNBC tumors, SL-145 potently suppressed tumor growth, angiogenesis, and metastases concomitant with dysregulation of the JAK2/STAT3 signaling pathway. Our findings highlight the potential of SL-145 in suppressing metastatic TNBC independent of the HSR.
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Collections - Graduate School > Department of Biomedical Sciences > 1. Journal Articles
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