An overview of topoisomerase I-targeting agents.
The camptothecins are a new class of antitumor agents that target topoisomerase I. Irinotecan and topotecan are the most widely used camptothecin analogs in clinical practice, with documented clinical activity in colorectal and ovarian cancer. Ongoing clinical trials with these agents are further characterizing their spectra of clinical activity and determining their optimal schedule of administration in combination with other anticancer agents. Newer camptothecin analogs in clinical development, such as 9-aminocamptothecin, 9-nitrocamptothecin, GI1147211, and DX-8951f, are also being studied to determine if they have improved toxicity and efficacy profiles compared with existing analogs. The successful development of the camptothecins as antitumor agents demonstrates the importance of topoisomerase 1 as a target for cancer chemotherapy.
Arbuck
S G
SG
Division of Cancer Treatment, Diagnosis, and Centers, National Cancer Institute, Bethesda Naval Hospital, MD 20892, USA.
Takimoto
C H
CH
D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004264:DNA Topoisomerases, Type I / Q000502:physiology*; D019008:Drug Resistance, Neoplasm; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D000077146:Irinotecan; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology*; D059004:Topoisomerase I Inhibitors; D019772:Topotecan / Q000494:pharmacology* / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D059004:Topoisomerase I Inhibitors; D000077146:Irinotecan; D019772:Topotecan; D004264:DNA Topoisomerases, Type I; D002166:Camptothecin