title: The evolving use of arsenic in pharmacotherapy of malignant disease.
abstract: For more than 2,000 years, arsenic and its derivatives have shown medical utility. Owing to the toxicities and potential carcinogenicity of arsenicals, their popularity has fluctuated. The exact mechanism of action of therapeutic arsenic is not well characterized but likely to involve apoptosis, generation of reactive oxygen species, inhibition of intracellular transduction pathways, and cell functions. Arsenic trioxide has received approval for use in patients with relapsed acute promyelocytic leukemia for remission induction. Arsenic has additionally shown activity in a range of solid tumors, myelodysplastic syndrome, multiple myeloma, and in autoimmune diseases. The following is a review of the history of arsenic, its cellular metabolism, pharmacology, genetic basis of disposition, associated toxicities, and clinical efficacy.
authors.affiliation: Hofstra North Shore-LIJ School of Medicine, 300 Community Drive Manhasset, New York, NY 11030, USA. akritharis@nshs.edu
authors.forename: Athena
authors.initials: A
authors.lastname: Kritharis
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Bradley
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Budman
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D020261:Arsenic Poisoning / Q000175:diagnosis / Q000209:etiology; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001711:Biotransformation / Q000235:genetics / Q000502:physiology; D002986:Clinical Trials as Topic; D003924:Diabetes Mellitus, Type 2 / Q000139:chemically induced; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D005786:Gene Expression Regulation / Q000187:drug effects; D006331:Heart Diseases / Q000139:chemically induced; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy; D007964:Leukocytosis / Q000139:chemically induced; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000139:chemically induced / Q000188:drug therapy*; D010087:Oxides / Q000009:adverse effects / Q000627:therapeutic use; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001152:Arsenicals; D010087:Oxides; D017382:Reactive Oxygen Species; D008780:Methyltransferases; C505756:AS3MT protein, human; D000077237:Arsenic Trioxide