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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2022-05-02

AUTHORS

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

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. More... »

PAGES

1-9

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41388-022-02269-y

    DOI

    http://dx.doi.org/10.1038/s41388-022-02269-y

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1147542377

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/35501463


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