Receptor induction and targeted drug delivery: a new antileukaemia strategy.
Strategic modalities of drug delivery have the potential to greatly improve the therapeutic efficacy of available drugs in acute myelogenous leukaemia (AML). Folate receptor (FR) type beta is selectively expressed on the surface of approximately 70% of AMLs. Increased FR-beta expression in these cells can be induced by all-trans retinoic acid (ATRA) and other retinoid compounds in the absence of terminal differentiation or cell growth inhibition. An apparent post-transcriptional modification prevents FR-beta in normal haematopoietic cells from binding folate, in contrast to AML cells. FR-beta may, therefore, be used as a target for the selective delivery of chemotherapeutic drugs to AML cells; this treatment modality appears to be particularly efficacious when administered in conjunction with retinoid-induction of FR-beta. FR-targeted liposomal drug delivery can also bypass the P-glycoprotein (P-gp)-mediated drug efflux pump commonly associated with multiple drug resistance in AML. The rationale and merits of this novel experimental treatment for AML and the current status of this research are provided.
Ratnam
Manohar
M
Department of Biochemistry and Molecular Biology, Medical College of Ohio, 3035 Arlington Ave, Toledo, OH 43614-5804, USA. mratnam@mco.edu
Hao
Hong
H
Zheng
Xuan
X
Wang
Hui
H
Qi
Huiling
H
Lee
Robert
R
Pan
Xing
X
D000818:Animals; D018943:Anthracyclines / Q000008:administration & dosage / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation / Q000379:methods; D002352:Carrier Proteins / Q000187:drug effects* / Q000235:genetics; D004317:Doxorubicin / Q000008:administration & dosage / Q000627:therapeutic use; D016503:Drug Delivery Systems; D058973:Folate Receptors, GPI-Anchored; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D011956:Receptors, Cell Surface / Q000187:drug effects* / Q000235:genetics; D014158:Transcription, Genetic
D018943:Anthracyclines; D000970:Antineoplastic Agents; D002352:Carrier Proteins; D058973:Folate Receptors, GPI-Anchored; D011956:Receptors, Cell Surface; D004317:Doxorubicin