title: Agents targeting the Hedgehog pathway for pancreatic cancer treatment.
abstract: Recent evidence has demonstrated that aberrant reactivation of the Hedgehog signaling pathway contributes to tumor initiation and progression in various human malignancies, including pancreatic cancer; therefore, the Hedgehog pathway has emerged as a promising novel therapeutic target. Initial translational studies conducted using cyclopamine, a small-molecule inhibitor of the Smoothened (SMO) component of the Hedgehog pathway, demonstrated that pharmacological blockade of aberrant Hedgehog signaling has the potential to inhibit tumor initiation, progression and metastatic spread. This concept has been corroborated using different compounds in various preclinical models of pancreatic cancer and other malignancies; several of these studies suggest possible therapeutic synergisms of Hedgehog inhibitors with established antineoplastic agents. This review provides a concise overview of translational studies assessing the use of Hedgehog inhibitors as novel therapeutic strategy for cancer, particularly pancreatic cancer.
authors.affiliation: Department of Internal Medicine 3, Center of Integrated Oncology Cologne-Bonn, University of Bonn, Wilhelmstrasse 35-37, Bonn, Germany.
authors.forename: Savita
authors.initials: S
authors.lastname: Bisht
authors.forename: Peter
authors.initials: P
authors.lastname: Brossart
authors.forename: Anirban
authors.initials: A
authors.lastname: Maitra
authors.forename: Georg
authors.initials: G
authors.lastname: Feldmann
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D021441:Carcinoma, Pancreatic Ductal / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002986:Clinical Trials as Topic; D053823:Hedgehog Proteins / Q000378:metabolism*; D006801:Humans; D010179:Pancreas / Q000378:metabolism / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D053823:Hedgehog Proteins