A novel HSP90 inhibitor SL-145 suppresses metastatic triple-negative breast cancer without triggering the heat shock response

Ji Young Kim, Tae Min Cho, Jung Min Park, Soeun Park, Minsu Park, Kee Dal Nam, Dongmi Ko, Juyeon Seo, Seongjae Kim, Eunsun Jung, Lee Farrand, Cong Truong Nguyen, Van Hai Hoang, Minh Thanh La, Jihyae Ann, Gibeom Nam, Hyun Ju Park, Jeewoo Lee, Yoon Jae Kim, Jae Hong Seo

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)3289-3297
Number of pages9
JournalOncogene
Volume41
Issue number23
DOIs
Publication statusPublished - 2022 Jun 3

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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