title: Advances in Smoothened-targeting therapies for pancreatic cancer: implication for drug discovery from herbal medicines.
abstract: Smoothened (SMO) is a member of sonic hedgehog homology (SHH) signaling pathway. It plays a key role as a bridge between patched-1 (PTCH-1) and Gli. Aberrant SHH expression can be detected in various malignant tissues, and the expression in pancreatic cancer stem cells is higher apparently. SHH signals are closely associated with self-duplication of cancer stem cells, formation of tumor vessels as well as matrixes. SMO antagonists such as cyclopamine, GDC-0449 and so on show potential to inhibit activity of SHH signaling, and arrest the growth as well as metastases of tumors. Recently, a few of SMO antagonists have been studied in phase I clinical trials and some are in phase II, meanwhile, phase I or II trials of SMO antagonists to treat pancreatic cancer are performed currently. As the classical SMO antagonist, cyclopamine is extracted from a medicinal plant. Perhaps researchers may be able to determine more effective SMO-targeting drugs from herbal medicines in the future.
authors.affiliation: Department of Integrative Oncology, Shanghai Cancer Center, Fudan University, China.
authors.forename: Jin-bin
authors.initials: JB
authors.lastname: Han
authors.forename: Yong-qiang
authors.initials: YQ
authors.lastname: Hua
authors.forename: Lian-yu
authors.initials: LY
authors.lastname: Chen
authors.forename: Lu-ming
authors.initials: LM
authors.lastname: Liu
mesh_terms: D055808:Drug Discovery; D004365:Drugs, Chinese Herbal; D053823:Hedgehog Proteins / Q000378:metabolism; D006801:Humans; D014411:Neoplastic Stem Cells; D010190:Pancreatic Neoplasms / Q000188:drug therapy; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors*; D015398:Signal Transduction; D000072086:Smoothened Receptor; D014704:Veratrum Alkaloids / Q000494:pharmacology
chemical_list: D004365:Drugs, Chinese Herbal; D053823:Hedgehog Proteins; D043562:Receptors, G-Protein-Coupled; C509239:SHH protein, human; C491023:SMO protein, human; D000072086:Smoothened Receptor; D014704:Veratrum Alkaloids; C000541:cyclopamine