Multidrug resistance in AIDS-related lymphoma.
OBJECTIVE
AIDS-related lymphoma has a decreased response rate and poorer prognosis to standard chemotherapy when compared with lymphoma in the non-HIV population. In addition to the known HIV-related and lymphoma-related poor prognostic factors, this review discusses another factor, MDR-1 expression and its impact on response to therapy in patients with AIDS-related lymphoma.


RESULTS
There is an increased incidence of de-novo MDR-1 expression in AIDS-related lymphoma compared with lymphoma in the non-HIV settings. MDR-1 expression in AIDS-related lymphoma is associated with poor response to conventional combination chemotherapy. Liposomal encapsulation of doxorubicin when substituted for doxorubicin in the CHOP regimen (cyclophosphamide, doxorubicin, vincristine, prednisone) seems to overcome P-glycoprotein-mediated drug resistance in AIDS-related lymphoma.


CONCLUSIONS
The overexpression of MDR-1 gene product P-glycoprotein is an adverse prognostic factor in AIDS-related lymphoma. Treatment with liposomal encapsulated doxorubicin seems to overcome the P-glycoprotein-related drug resistance. This and other strategies to modulate MDR-1 should be further explored in order to improve success rates in the treatment of AIDS-related lymphoma.
Tulpule
Anil
A
Division of Hematology, Department of Medicine, University of Southern California, Keck School of Medicine, Norris Cancer Center, 1441 Eastlake Avenue, Los Angeles, CA 90033, USA. tulpule@usc.edu
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage / Q000627:therapeutic use; D024921:Drug Resistance, Multiple, Viral / Q000187:drug effects / Q000235:genetics*; D015967:Gene Expression Regulation, Viral / Q000187:drug effects / Q000235:genetics; D019450:Genes, MDR / Q000187:drug effects / Q000235:genetics; D006801:Humans; D008081:Liposomes; D016483:Lymphoma, AIDS-Related / Q000188:drug therapy* / Q000235:genetics*; D011241:Prednisone / Q000008:administration & dosage; D011379:Prognosis; D014750:Vincristine / Q000008:administration & dosage
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic; D008081:Liposomes; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone