Recent advances in the clinical targeting of hedgehog/GLI signaling in cancer

Hao Xie; Brooke D. Paradise; Wen Wee Ma; Martin E. Fernandez-Zapico

doi:10.3390/cells8050394

Recent advances in the clinical targeting of hedgehog/GLI signaling in cancer

Hao Xie, Brooke D. Paradise, Wen Wee Ma, Martin E. Fernandez-Zapico

Research output: Contribution to journal › Review article › peer-review

Abstract

The Hedgehog/GLI signaling pathway plays an important role in normal embryonic tissue development and has been implicated in the pathogenesis of various human cancers. In this review article, we summarize pre-clinical evidence supporting the suitability of targeting this signaling pathway in cancers. We review agents blocking both the ligand-dependent and ligand-independent cascades, and discuss the clinical evidence, which has led to the FDA approval of Hedgehog receptor Smoothened inhibitors, vismodegib, and sonidegib, in different malignancies. Finally, we provide an overview of published and ongoing clinical trial data on single agent or combination therapeutic strategies, targeting Hedgehog/GLI signaling pathway, in both advanced solid tumors and hematologic malignancies.

Original language	English (US)
Article number	394
Journal	Cells
Volume	8
Issue number	5
DOIs	https://doi.org/10.3390/cells8050394
State	Published - May 2019

Keywords

Clinical trials
GLI factors
Hedgehog
Smoothened
Sonidegib
Vismodegib

ASJC Scopus subject areas

General Medicine

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10.3390/cells8050394

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title = "Recent advances in the clinical targeting of hedgehog/GLI signaling in cancer",

abstract = "The Hedgehog/GLI signaling pathway plays an important role in normal embryonic tissue development and has been implicated in the pathogenesis of various human cancers. In this review article, we summarize pre-clinical evidence supporting the suitability of targeting this signaling pathway in cancers. We review agents blocking both the ligand-dependent and ligand-independent cascades, and discuss the clinical evidence, which has led to the FDA approval of Hedgehog receptor Smoothened inhibitors, vismodegib, and sonidegib, in different malignancies. Finally, we provide an overview of published and ongoing clinical trial data on single agent or combination therapeutic strategies, targeting Hedgehog/GLI signaling pathway, in both advanced solid tumors and hematologic malignancies.",

keywords = "Clinical trials, GLI factors, Hedgehog, Smoothened, Sonidegib, Vismodegib",

author = "Hao Xie and Paradise, {Brooke D.} and Ma, {Wen Wee} and Fernandez-Zapico, {Martin E.}",

note = "Publisher Copyright: {\textcopyright} 2019 by the authors. Licensee MDPI, Basel, Switzerland.",

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AU - Paradise, Brooke D.

AU - Ma, Wen Wee

AU - Fernandez-Zapico, Martin E.

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N2 - The Hedgehog/GLI signaling pathway plays an important role in normal embryonic tissue development and has been implicated in the pathogenesis of various human cancers. In this review article, we summarize pre-clinical evidence supporting the suitability of targeting this signaling pathway in cancers. We review agents blocking both the ligand-dependent and ligand-independent cascades, and discuss the clinical evidence, which has led to the FDA approval of Hedgehog receptor Smoothened inhibitors, vismodegib, and sonidegib, in different malignancies. Finally, we provide an overview of published and ongoing clinical trial data on single agent or combination therapeutic strategies, targeting Hedgehog/GLI signaling pathway, in both advanced solid tumors and hematologic malignancies.

AB - The Hedgehog/GLI signaling pathway plays an important role in normal embryonic tissue development and has been implicated in the pathogenesis of various human cancers. In this review article, we summarize pre-clinical evidence supporting the suitability of targeting this signaling pathway in cancers. We review agents blocking both the ligand-dependent and ligand-independent cascades, and discuss the clinical evidence, which has led to the FDA approval of Hedgehog receptor Smoothened inhibitors, vismodegib, and sonidegib, in different malignancies. Finally, we provide an overview of published and ongoing clinical trial data on single agent or combination therapeutic strategies, targeting Hedgehog/GLI signaling pathway, in both advanced solid tumors and hematologic malignancies.

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Recent advances in the clinical targeting of hedgehog/GLI signaling in cancer

Abstract

Keywords

ASJC Scopus subject areas

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