title: A new era for an ancient drug: arsenic trioxide and Hedgehog signaling.
abstract: Arsenic has been used for ages as a therapeutic agent. Currently, it is an FDA approved drug to treat acute promyelocytic leukemia where it leads to degradation of the PML-RAR fusion protein. It has been shown to have various other targets in cells such as JNK, NFκB, thioredoxin reductase, and MAPK pathways. Most of its effects in cells have been through arsenic's ability to bind to thiol groups in cysteine residues. Recent evidence has shown that arsenic can inhibit the Hedgehog pathway by inhibiting GLI proteins. The proposed mechanism of action is through direct binding. Potential binding sites include the critical cysteine residues in GLI zinc finger domains. The role of the Hedgehog pathway has been implicated in many cancers such as basal cell carcinoma, medulloblastoma, Ewing sarcoma, and rhabdoid tumors. Current Hedgehog pathway inhibitors have been fraught with resistance issues and so arsenic trioxide may provide an alternative therapy when combined with these other inhibitors or after acquired resistance.
authors.affiliation: Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, District of Columbia, USA.
authors.forename: Elspeth M
authors.initials: EM
authors.lastname: Beauchamp
authors.forename: Aykut
authors.initials: A
authors.lastname: Uren
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy*; D002528:Cerebellar Neoplasms / Q000188:drug therapy* / Q000473:pathology; D053823:Hedgehog Proteins / Q000494:pharmacology; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000473:pathology; D008527:Medulloblastoma / Q000188:drug therapy* / Q000473:pathology; D015513:Oncogene Proteins / Q000494:pharmacology*; D010087:Oxides / Q000494:pharmacology / Q000627:therapeutic use*; D012512:Sarcoma, Ewing / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; D001152:Arsenicals; D053823:Hedgehog Proteins; D015513:Oncogene Proteins; D010087:Oxides; D000077237:Arsenic Trioxide