Hedgehog Signaling: From Basic Biology to Cancer Therapy.

Fujia Wu, Yu Zhang, Bo Sun, Andrew P McMahon, Yu Wang

Journal: Cell chemical biology 2017;24(3):252-280

PMID: 28286127

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Abstract

The Hedgehog (HH) signaling pathway was discovered originally as a key pathway in embryonic patterning and development. Since its discovery, it has become increasingly clear that the HH pathway also plays important roles in a multitude of cancers. Therefore, HH signaling has emerged as a therapeutic target of interest for cancer therapy. In this review, we provide a brief overview of HH signaling and the key molecular players involved and offer an up-to-date summary of our current knowledge of endogenous and exogenous small molecules that modulate HH signaling. We discuss experiences and lessons learned from the decades-long efforts toward the development of cancer therapies targeting the HH pathway. Challenges to develop next-generation cancer therapies are highlighted.

Address: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.; State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.; Department of Stem Cell Biology and Regenerative Medicine, Eli and Edythe Broad-CIRM Center for Regenerative Medicine and Stem Cell Research, W.M. Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.; State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: [email protected].

DOI: 10.1016/j.chembiol.2017.02.010

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MeSH Terms: Antineoplastic Agents, Cilia, Hedgehog Proteins, Humans, Kruppel-Like Transcription Factors, Neoplasms, Oxysterols, Phosphatidylinositol Phosphates, Signal Transduction, Small Molecule Libraries, Smoothened Receptor