title: Hedgehog signaling in prostate cancer and its therapeutic implication.
abstract: Activation of Hedgehog (Hh) signaling is implicated in the development and progression of several tumor types, including prostate cancer, which is still the most common non-skin malignancy and the third leading cause of cancer-related mortality in men in industrialized countries worldwide. Several studies have indicated that the Hh pathway plays a crucial role in the development as well as in the progression of this disease to more aggressive and even therapy-resistant disease states. Moreover, preclinical data have shown that inhibition of Hh signaling has the potential to reduce prostate cancer invasiveness and metastatic potential. Clinical trials investigating the benefit of Hh inhibitors in patients with prostate cancer have recently been initiated. However, acquired drug resistance has already been observed in other tumor types after long-term Hh inhibition. Therefore, combining Hh inhibitors with ionizing radiation, chemotherapy or other molecular targeted agents could represent an alternative therapeutic strategy. In this review, we will highlight the role of Hh signaling in the development and progression of prostate cancer and summarize the different therapeutic applications of Hedgehog inhibition.
authors.affiliation: Laboratory of Experimental Radiotherapy, Department of Oncology, KU Leuven, & Radiation Oncology, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium. annelies.gonnissen@med.kuleuven.be
authors.forename: Annelies
authors.initials: A
authors.lastname: Gonnissen
authors.forename: Sofie
authors.initials: S
authors.lastname: Isebaert
authors.forename: Karin
authors.initials: K
authors.lastname: Haustermans
mesh_terms: D000813:Anilides / Q000627:therapeutic use; D000818:Animals; D002280:Basal Cell Carcinoma / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy; D003131:Combined Modality Therapy; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011494:Protein Kinases / Q000737:chemistry / Q000378:metabolism; D011725:Pyridines / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use; D015398:Signal Transduction
chemical_list: D000813:Anilides; C551027:GANT 61; D053823:Hedgehog Proteins; C538724:HhAntag691; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D011743:Pyrimidines; D011494:Protein Kinases