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dc.contributor.authorD'Arcy, Nicholas
dc.contributor.authorGabrielli, Brian
dc.date.accessioned2021-09-21T04:39:33Z
dc.date.available2021-09-21T04:39:33Z
dc.date.issued2017
dc.identifier.issn0929-8673
dc.identifier.doi10.2174/0929867323666161205122613
dc.identifier.urihttp://hdl.handle.net/10072/408172
dc.description.abstractInteractions between the decatenation checkpoint and Topoisomerase II (TopoII) are vital for maintaining integrity of the genome. Agents that target this enzyme have been in clinical use in cancer therapy for over 30 years with great success. The types of compounds that have been developed to target TopoII are broadly divided into poisons and catalytic inhibitors. The TopoII poisons are in clinical use as anti-cancer therapies, although in common to most chemotherapeutic agents, they display considerable normal tissue toxicity. Inhibition of the TopoIIß isoform has been implicated in this cytotoxicity. Response to TopoII active agents is determined by several factors, but cell cycle checkpoints play a large role in sensitivity and resistance. The G2/M phase checkpoints are of particular importance in considering the effectiveness of these drugs and are reviewed in this article. Functionality of the ATM dependent decatenation checkpoint may represent a new avenue for selective cancer therapy. Here we review the function of TopoII, the anti-cancer mechanisms and limitations of current catalytic inhibitors and poisons, and their influence on cell cycle checkpoints. We will also assess potential new mechanisms for targeting this enzyme to limit normal tissue toxicity, and how the cell cycle checkpoint triggered by these drugs may provide an alternative and possibly better target for novel therapies.
dc.description.peerreviewedYes
dc.languageEnglish
dc.publisherBentham Science Publishers
dc.relation.ispartofpagefrom1504
dc.relation.ispartofpageto1519
dc.relation.ispartofissue15
dc.relation.ispartofjournalCurrent Medicinal Chemistry
dc.relation.ispartofvolume24
dc.subject.fieldofresearchMedicinal and biomolecular chemistry
dc.subject.fieldofresearchBiochemistry and cell biology
dc.subject.fieldofresearchPharmacology and pharmaceutical sciences
dc.subject.fieldofresearchcode3404
dc.subject.fieldofresearchcode3101
dc.subject.fieldofresearchcode3214
dc.subject.keywordsScience & Technology
dc.subject.keywordsLife Sciences & Biomedicine
dc.subject.keywordsBiochemistry & Molecular Biology
dc.subject.keywordsChemistry, Medicinal
dc.subject.keywordsPharmacology & Pharmacy
dc.titleTopoisomerase II inhibitors and poisons, and the influence of cell cycle checkpoints
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationD'Arcy, N; Gabrielli, B, Topoisomerase II inhibitors and poisons, and the influence of cell cycle checkpoints, Current Medicinal Chemistry, 2017, 24 (15), pp. 1504-1519
dcterms.dateAccepted2016-11-03
dc.date.updated2021-09-21T04:37:50Z
gro.hasfulltextNo Full Text
gro.griffith.authorGabrielli, Brian


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