Drug delivery in acute myeloid leukemia.
BACKGROUND
Acute myeloid leukemia was among the first malignancies to be cured by drug therapy alone, but overall survival rates remain unsatisfactory and have changed little over the past 20 years. Conventional chemotherapeutic regimens, which almost invariably include cytarabine and anthracyclines, are untargeted, and more specific therapies are needed.


OBJECTIVE
We have chosen acute myeloid leukemia as a disease prototype to review established and novel targeted approaches in leukemia treatment.


METHODS
Our selection of the reviewed literature focused on drug delivery aspects.


CONCLUSIONS
While the toxicity profile of chemotherapeutics has been improved by liposomal formulations and antibody conjugation for leukemia-directed uptake, their efficacy has probably not changed significantly. Drugs with an alternative mode of action, including kinase inhibitors, hold great promise. Further improvements may result from the characterization of novel acute myeloid leukemia (AML) cell surface receptors and of leukemic stem cells, as well as from the design of leukemia-targeted gene therapy vectors.
University Medical Center Hamburg-Eppendorf, Department of Oncology and Hematology, Martinistrasse 52, D-20246 Hamburg, Germany.
Johannes
J
Kohlschütter
Stefan
S
Michelfelder
Martin
M
Trepel
D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D015703:Antigens, CD / Q000276:immunology; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D016503:Drug Delivery Systems; D015316:Genetic Therapy; D006801:Humans; D039041:Integrin alpha4beta1 / Q000037:antagonists & inhibitors; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy; D008081:Liposomes; D014411:Neoplastic Stem Cells / Q000187:drug effects; D063268:Sialic Acid Binding Ig-like Lectin 3
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000970:Antineoplastic Agents; C571163:CD33 protein, human; D039041:Integrin alpha4beta1; D008081:Liposomes; D063268:Sialic Acid Binding Ig-like Lectin 3