title: Hedgehog Signaling: From Basic Biology to Cancer Therapy.
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.
authors.affiliation: 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.
authors.forename: Fujia
authors.initials: F
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Sun
authors.affiliation: 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.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: McMahon
authors.affiliation: 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: wangyu@ioz.ac.cn.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D002923:Cilia / Q000378:metabolism; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D000072376:Oxysterols / Q000737:chemistry / Q000378:metabolism; D018129:Phosphatidylinositol Phosphates / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D054852:Small Molecule Libraries / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D000072086:Smoothened Receptor / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; D000072376:Oxysterols; D018129:Phosphatidylinositol Phosphates; D054852:Small Molecule Libraries; D000072086:Smoothened Receptor; C037178:phosphatidylinositol 4-phosphate
keywords: GLI; basal cell carcinoma; cancer therapy; cholesterol; drug resistance; endogenous smoothened regulation; hedgehog signaling; medulloblastoma; smoothened; stem cell