Is p-glycoprotein a potential target for reversing clinical drug resistance?
The overexpression of MDR1 p-glycoprotein has been associated with the emergence of clinical drug resistance for a number of malignancies, especially those of the hematopoietic variety. Given this observation, the question arises regarding the suitability of p-glycoprotein as a target for reversing multiple drug resistance (MDR) and improving therapeutic outcome. This review focuses on the role of p-glycoprotein in hematopoietic malignancies and proposes that these malignancies serve as a prototype for further investigations. The status of clinical studies to reverse or circumvent clinical MDR is also discussed. Recommendations are made regarding the kinds of tumors to be studied, the type of chemosensitizer desired, and the design of clinical protocols required to answer the question of whether p-glycoprotein is a suitable target to reverse or prevent clinical MDR.
Dalton
W S
WS
University of Arizona, College of Medicine, Arizona Cancer Center, Tucson 85724.
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis*; D000208:Acute Disease; D018432:Drug Resistance, Multiple; D006801:Humans; D007951:Leukemia, Myeloid / Q000378:metabolism; D008228:Lymphoma, Non-Hodgkin / Q000737:chemistry; D009101:Multiple Myeloma / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1