Topoisomerase I interactive agents.

Abstract

Increased insight into the mechanism of interaction of topoisomerase I interactive agents will maximize the therapeutic index and enhance the development of additional agents. Preclinical studies designed to elucidate mechanisms by which the topoisomerase I interactive agents induce cell death will be essential. The role of ABC transporters in resistance to topoisomerase I interactive agents has been recently appreciated and future studies should be directed at circumventing this resistance. The results of preclinical studies must be translated into the design of clinical trials so that these agents can be used rationally. In this regard results of preclinical studies have clearly pointed to the enhanced antitumor activity from protracted dosing of topoisomerase I interactive agents and results of clinical trials are now supporting these preclinical findings. Finally, investigators are trying to understand better the mechanism(s) of the dose-limiting toxicities observed with the currently available topoisomerase I interactive agents in an effort to enable the optimal dosing of these agents. Even though the first priority must be to determine the therapeutic potential of the currently available agents, it is reassuring to know that other topoisomerase I interactive agents are currently under development.