[Cyclosporine as drug resistance modifiers; mechanism and clinical investigation].
Multidrug resistance(MDR), mediated by P-glycoprotein, is a well-understood mechanism of resistance to anticancer drugs. P-glycoprotein is thought to act as an efflux pump with broad specificity for variety of anticancer drugs. Cyclosporine and its analogue, SDZ PSC 833, have demonstrated ability to inhibit P-glycoprotein mediated transport function, restore accumulation defects for anticancer drugs, and reverse resistance in vitro and in vivo. The clinical trials of these drugs are on going. P-glycoprotein may also play a pivotal role in the evolution of pharmacological defence mechanisms, protecting organisms from cytotoxic agents. Approach to overcome resistance may result in serious challenges to the host's natural defenses. Clinical trials of MDR modulators, such as cyclosporine or SDZ PSC 833, should be designed with caution and with careful consideration for potential pharmacokinetic and pharmacodynamic interaction.
Hama
S
S
Pharmacology division, National Cancer Center Research Institute, Hiroshima University School of Medicine.
Kurisu
K
K
Saijo
N
N
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000502:physiology; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D001692:Biological Transport / Q000187:drug effects; D002986:Clinical Trials as Topic; D016572:Cyclosporine / Q000494:pharmacology* / Q000627:therapeutic use; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D016572:Cyclosporine