A novel HSP90 inhibitor SL-145 suppresses metastatic triple-negative breast cancer without triggering the heat shock response
- Authors
- Kim, Ji Young; Cho, Tae-Min; Park, Jung Min; Park, Soeun; Park, Minsu; Nam, Kee Dal; 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
- Jun-2022
- Publisher
- Nature Publishing Group
- Citation
- Oncogene, v.41, no.23, pp 3289 - 3297
- Pages
- 9
- Indexed
- SCIE
SCOPUS
- Journal Title
- Oncogene
- Volume
- 41
- Number
- 23
- Start Page
- 3289
- End Page
- 3297
- URI
- https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/60690
- DOI
- 10.1038/s41388-022-02269-y
- ISSN
- 0950-9232
1476-5594
- 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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- Appears in
Collections - 2. Clinical Science > Department of Medical Oncology and Hematology > 1. Journal Articles
- 3. Graduate School > Graduate School > 1. Journal Articles
- 4. Research institute > Cancer Institute > 1. Journal Articles
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