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• W4306988968 abstract "Overview Topoisomerases are an important class of enzymes that are ubiquitously expressed across all organisms, and function to resolve deoxyribonucleic acid (DNA) supercoiling and prevent and resolve ribonucleic acid (RNA) entanglements. These biochemically distinct enzymes play a critical role in DNA replication, transcription, and cellular division. Inhibitors that target specific topoisomerases, therefore, represent a major component of the anticancer chemotherapeutic armamentarium. In this chapter, we provide an overview of topoisomerase biology and topoisomerase inhibitors. We review the common and specific mechanisms of action and the molecular pharmacology of the drugs that target the topoisomerase cleavage complexes by interfacial inhibition. Molecular pathways for cancer cell death and DNA repair associated with each specific topoisomerase inhibitor are discussed. Other mechanisms of anticancer activity of selected topoisomerase inhibitors that include DNA intercalation and/or generation of oxygen radicals destabilizing and damaging chromatin structure are described. We summarize the clinical use, toxicity profile, and the molecular basis of sensitivity and resistance to topoisomerase inhibitors. We also discuss the pharmacogenomics focusing on genetic variants in drug‐metabolizing enzymes, transporters, and other proteins associated with topoisomerase inhibitors. Evolving data demonstrate the important role of molecular profiling and analysis of genetic variants in individuals that enable personalized dosing and enhance therapeutic efficacy, minimizing toxicity. Ongoing efforts focus on optimization of treatment selection, identification of novel combination therapies, elucidation of the molecular basis of response and resistance, and development of strategies for tumor‐targeted delivery based on tumor molecular signatures." @default.
• W4306988968 created "2022-10-22" @default.
• W4306988968 creator A5013592290 @default.
• W4306988968 creator A5042114293 @default.
• W4306988968 creator A5064625461 @default.
• W4306988968 creator A5074644543 @default.
• W4306988968 date "2022-10-21" @default.
• W4306988968 modified "2023-09-26" @default.
• W4306988968 title "<scp>DNA</scp> Topoisomerase Targeting Drugs" @default.
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