title: Emerging from their burrow: Hedgehog pathway inhibitors for cancer.
abstract: BACKGROUND
  Cancer treatment is moving away from conventional cytotoxic drugs and towards agents that target specific proteins and mechanisms important to cancer development or survival. The Hedgehog Pathway (HhP) is a signal transduction pathway and its constitutive activation is tumorigenic in basal cell carcinoma (BCC). The HhP enables phenotypic flexibility, and channels tumor-stroma interactions. As a result, it is over-expressed in numerous cancers as well as in the tumor microenvironment and may represent a promising therapeutic target.
  
  
  METHODS
  In this article, we review the rationale for targeting HhP and its role as an oncogenic driver, in tumor epithelial-to-mesenchymal transition (EMT), and in the tumor microenvironment and describe the results of preclinical and clinical studies involving HhP inhibitors.
  
  
  CONCLUSIONS
  HhP activation plays an important role in both the tumor microenvironment and tumor EMT which can lead to treatment resistance for a number of different malignancies. In addition to standard use in BCC, several HhP inhibitors are in preclinical, early, and mid-stage clinical development for other solid and hematologic malignancies.
authors.affiliation: a Section of Radiation Oncology, Department of Internal Medicine , University of New Mexico School of Medicine , Albuquerque , NM , USA.
authors.forename: Gregory N
authors.initials: GN
authors.lastname: Gan
authors.affiliation: b Division of Medical Oncology, Department of Medicine , University of Colorado School of Medicine , Aurora , CO , USA.|c Charles C. Gates Center for Stem Cell Biology , University of Colorado School of Medicine , Aurora , CO , USA.|d Department of Otolaryngology , University of Colorado School of Medicine , Aurora , CO , USA.
authors.forename: Antonio
authors.initials: A
authors.lastname: Jimeno
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015195:Drug Design; D019008:Drug Resistance, Neoplasm; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D059016:Tumor Microenvironment / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D053823:Hedgehog Proteins
keywords: Epithelial-to-mesenchymal transition; Hedgehog inhibitors; Hedgehog pathway; tumor microenvironment