Human colon tumor xenografts are known to be refractory to most chemotherapeutic anticancer drugs. Recent studies have demonstrated that a class of topoisomerase I inhibitors, camptothecins, exhibits unprecedented antitumor activity against human colon tumor xenografts in nude mice (Giovanella et al., 1989; Potmesil c? al., 1991). The ability of camptothecin to overcome MDR 1 -mediated resistance may be one important contributing factor to camptothecin's impressive activity (Chen et al., 1991). If this interpretation is correct, it will be promising to develop new drugs that can overcome MDR1-mediated resistance for treating certain human solid tumors. Admittedly, MDR1-mediated resistance is only one of the many mechanisms of drug resistance in tumor cells. Designing new drugs for various resistant tumors will require fundamental information on various drug resistance mechanisms. It will eventually be possible to tailor drugs for particular drug-resistant tumors. Using topoisomerase inhibitors, we have begun to understand some of the parameters that may have to be considered for rational drug design.
ASJC Scopus subject areas