Topoisomerases: therapeutic value].

P Faure, I Madelaine

Pharmacie, Hôpital Saint-Louis, Paris.

Annales pharmaceutiques françaises 1996

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Anticancer pharmacology offers rich prospects for future therapeutic design. Knowledge of antitumoral agents pharmacology have widely advanced: understanding of the molecular cytotoxic mechanism of available agents, discovery of new compounds with a different and no-interfering mechanism of action. Since ten years, the identification of a couple of nuclear enzyme, DNA-topoisomerases, has answered to this goal. These enzymes catalyse the topological changes of the double strand DNA, participating to vital processes of cell metabolism. These enzymes are now know to be the intracellular target of widely used cytotoxic agents (such as anthracycline, Etoposide, Teniposide for DNA topoisomerase II) and for two new compounds in clinical trials (irinotecan and topotecan, both analogues of camptothecin, for DNA-topoisomerase I). This two last molecules, currently in phase II development, are promising. They seem to be synergistic in combination with available anticancer agents, but this remains to be demonstrated. Other drugs, inhibiting both DNA-topoisomerases I and II, are yet investigating. Would they provide new answers for the future?