Recent Advances in the Clinical Targeting of Hedgehog/GLI Signaling in Cancer

被引：61

作者：

Xie, Hao ^{[1
]}

Paradise, Brooke D. ^{[2
]}

Ma, Wen Wee ^{[1
]}

Fernandez-Zapico, Martin E. ^{[2
]}

机构：

[1] Mayo Clin, Div Med Oncol, Rochester, MN 55905 USA

[2] Mayo Clin, Div Oncol Res, Schulze Ctr Novel Therapeut, Rochester, MN 55905 USA

来源：

CELLS | 2019年 / 8卷 / 05期

基金：

美国国家卫生研究院;

关键词：

Hedgehog; Smoothened; GLI factors; clinical trials; vismodegib; sonidegib; BASAL-CELL CARCINOMA; PHASE-II TRIAL; ORAL SMOOTHENED INHIBITOR; PATHWAY INHIBITOR; OPEN-LABEL; DOSE-ESCALATION; DOUBLE-BLIND; STANDARD CHEMOTHERAPY; SONIDEGIB LDE225; DRUG-RESISTANCE;

D O I：

10.3390/cells8050394

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页数：17

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