The Hedgehog Signaling Pathway: A Viable Target in Breast Cancer?

Cancers
Priyanka BhatejaBhuvaneswari Ramaswamy

Abstract

The hedgehog (Hh) pathway plays a key role in embryonic development and stem cell programs. Deregulation of the Hh pathway is a key driver of basal cell carcinoma, and therapeutic targeting led to approval of Hh inhibitor, vismodegib, in the management of this cancer. The Hh pathway is implicated in other malignancies including hormone receptor (HR+) positive and triple negative breast cancer (TNBC). Hh signaling, which is activated in human mammary stem cells, results in activation of glioma-associated oncogene (GLI) transcription factors. High GLI1 expression correlates with worse outcomes in breast cancer. Non-canonical GLI1 activation is one mechanism by which estrogen exposure promotes breast cancer stem cell proliferation and epithelial-mesenchymal transition. Tamoxifen resistant cell lines show aberrant activation of Hh signaling, and knockdown of Hh pathway inhibited growth of tamoxifen resistant cells. As in other cancers Hh signaling is activated by the PI3K/AKT pathway in these endocrine resistant cell lines. Hh pathway activation has also been reported to mediate chemotherapy resistance in TNBC via various mechanisms including paracrine signaling to tumor micro-environment and selective proliferation of cancer stem ...Continue Reading

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Citations

May 12, 2020·Frontiers in Molecular Biosciences·Deguang KongHeide L Ford
Jun 25, 2020·Cancer Metastasis Reviews·Belinda J Petri, Carolyn M Klinge
Jul 31, 2020·Cancer Prevention Research·Eun-Ryeong HahmShivendra V Singh
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May 18, 2021·Chemistry & Biodiversity·Han ChenXiaoling Lu
Jun 12, 2021·Cancer Cell International·Jing ChenAlexander Tobias Teichmann
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Oct 27, 2021·Breast Cancer Research and Treatment·Anton J LucanusGeorge W Yip
Nov 28, 2021·Investigational New Drugs·Meng ZhangXiaoyu Li

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Methods Mentioned

BETA
transgenic
xenografts
nuclear translocation
xenograft

Clinical Trials Mentioned

NCT02303041
NCT02027376
NCT02694224

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