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Drug resistance: still a daunting challenge to the successful treatment of AML.

Authors :
Shaffer BC
Gillet JP
Patel C
Baer MR
Bates SE
Gottesman MM
Source :
Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy [Drug Resist Updat] 2012 Feb-Apr; Vol. 15 (1-2), pp. 62-9. Date of Electronic Publication: 2012 Mar 11.
Publication Year :
2012

Abstract

Resistance to chemotherapy remains a challenging issue for patients and their physicians. P-glycoprotein (Pgp, MDR1, ABCB1), as well as a family of structurally and functionally related proteins, are plasma membrane transporters able to efflux a variety of substrates from the cell cytoplasm, including chemotherapeutic agents. The discovery of ABCB1 made available a potential target for pharmacologic down-regulation of efflux-mediated chemotherapy resistance. In patients with acute myeloid leukemia (AML), a neoplasm characterized by proliferation of poorly differentiated myeloid progenitor cells, leukemic cells often express ABCB1 at high levels, which may lead to the development of resistance to chemotherapy. Thus, AML seemed to be a likely cancer for which the addition of drug efflux inhibitors to the chemotherapeutic regimen would improve outcomes in patients. Despite this rational hypothesis, the majority of clinical trials evaluating this strategy have failed to reach a positive endpoint, most recently the Eastern Cooperative Oncology Group E3999 trial. Here we review data suggesting the importance of ABCB1 in AML, address the failure of clinical trials to support a therapeutic strategy aimed at modulating ABCB1-mediated resistance, and consider the type of research that should be conducted in this field going forward.<br /> (Published by Elsevier Ltd.)

Details

Language :
English
ISSN :
1532-2084
Volume :
15
Issue :
1-2
Database :
MEDLINE
Journal :
Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy
Publication Type :
Academic Journal
Accession number :
22409994
Full Text :
https://doi.org/10.1016/j.drup.2012.02.001