title: Doxorubicin and multidrug resistance.
abstract: The circumvention of P-glycoprotein function by pharmacologic agents is a major focus of clinical trials aimed at increasing the cytotoxicity of multidrug resistance-associated drugs, including doxorubicin. The success of this approach will likely depend on the clinical significance of P-glycoprotein expression, which has not yet been elucidated for the common solid tumors, and the ability to achieve effective levels of circumventing agents without dose-limiting toxicities. Initial clinical studies suggested that biologically relevant concentrations of multidrug resistance modulators, eg, cyclosporine, can be achieved. Because pharmacologic agents that inhibit drug efflux by P-glycoprotein are themselves pumped out of cells by the transporter, this approach may have an inherent barrier to success. Laboratory studies have suggested alternative strategies for circumventing P-glycoprotein action, eg, the use of monoclonal antibodies directed against P-glycoprotein and liposome-encapsulated drugs.
authors.affiliation: Fox Chase Cancer Center, Philadelphia, Pennsylvania.
authors.forename: G D
authors.initials: GD
authors.lastname: Kruh
authors.forename: L J
authors.initials: LJ
authors.lastname: Goldstein
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D002986:Clinical Trials as Topic; D004317:Doxorubicin / Q000494:pharmacology*; D004351:Drug Resistance / Q000235:genetics / Q000502:physiology; D006801:Humans; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000502:physiology; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D004317:Doxorubicin