title: A proteomic approach to identifying new drug targets (potentiating topoisomerase II poisons).
abstract: Topoisomerase II poisons are an established part of best clinical practice for the treatment of a number of solid tumours and haematological malignancies. However, toxicity and resistance to chemotherapeutic drugs often complicate the treatment. Furthermore, topoisomerase II poisons can also induce sister chromatid exchange, chromosomal recombination and chromosome aberrations and are associated with a significant risk of secondary leukaemia. It would therefore be of great clinical benefit if the efficacy of topoisomerase II inhibitors could be enhanced without the increased toxic side effects. It is proposed that clinical agents targeting topoisomerase II can be enhanced by inhibiting proteins that modulate topoisomerase II. The aim is to identify proteins, that by the nature of their interaction with topoisomerase II, represent putative drug targets.
authors.affiliation: School of Clinical Sciences, Division of Gastroenterology, University of Liverpool, Henry Wellcome Laboratory, Crown Street, Liverpool L69 3BX, UK. John.Jenkins@liverpool.ac.uk
authors.forename: J R
authors.initials: JR
authors.lastname: Jenkins
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002877:Chromosomes, Human; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors; D006360:Heat-Shock Proteins / Q000037:antagonists & inhibitors; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D010446:Peptide Fragments; D010766:Phosphorylation; D011506:Proteins / Q000037:antagonists & inhibitors*; D040901:Proteomics; D059005:Topoisomerase II Inhibitors; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D018841:HSP90 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D010446:Peptide Fragments; D011506:Proteins; D059005:Topoisomerase II Inhibitors; D016159:Tumor Suppressor Protein p53; C509415:p53 protein (325-355), human