title: New prospects for drug development: the hedgehog pathway revealed. Focus on hematologic malignancies.
abstract: The hedgehog (Hh) pathway is a critical regulator of vertebrate embryonic development and is involved in the function of processes such as stem cell maintenance and differentiation, tissue polarity and cell proliferation. Given how critical these functions are, it is not surprising that mutations in Hh pathway components are often implicated in the tumorigenesis of a variety of human cancers. Promotion of tumor growth has recently been shown by activated Hh signaling in the tumor itself, as well as by pathway activation within surrounding cells comprising the tumor microenvironment. Targeted disruption of various Hh pathway proteins has been successfully employed as an anticancer strategy with several synthetic Hh antagonists now available. Here, the molecular basis of Hh signaling, the therapeutic rationales for targeting this pathway and the current status of Hh pathway inhibitors in the clinic are reviewed.
authors: Hematology & Medical Oncology, Department of Internal Medicine, University of Miami, 1475 North West 12th Avenue, Miami, FL 33136, USA.
authors: Agustin
authors: A
authors: Pimentel
authors: Michel
authors: M
authors: Velez
authors: Luz J
authors: LJ
authors: Barahona
authors: Ronan
authors: R
authors: Swords
authors: Lazaros
authors: L
authors: Lekakis
mesh_terms: D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D053823:Hedgehog Proteins / Q000235:genetics* / Q000378:metabolism; D019337:Hematologic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D006801:Humans; D058990:Molecular Targeted Therapy; D009154:Mutation; D015398:Signal Transduction / Q000235:genetics
chemical_list: D053823:Hedgehog Proteins