Role of drug transport and metabolism in the chemoresistance of acute myeloid leukemia

被引:38
作者
Marin, Jose J. G. [1 ]
Briz, Oscar [1 ]
Rodriguez-Macias, Gabriela [2 ]
Diez-Martin, Jose L. [2 ,3 ]
Macias, Rocio I. R. [1 ]
机构
[1] Univ Salamanca, Lab Expt Hepatol & Drug Targeting HEVEFARM, IBSAL, Natl Inst Study Liver & Gastrointestinal Dis CIBE, E-37008 Salamanca, Spain
[2] Hosp Gen Univ Gregorio Maranon, Dept Hematol, BMT Unit, Madrid, Spain
[3] Gregorio Maranon Inst Hlth Res IISGM, Madrid, Spain
关键词
Biotransformation; Cancer; Chemotherapy; Drug efflux; Drug uptake; CANCER RESISTANCE PROTEIN; ACUTE MYELOGENOUS LEUKEMIA; ACUTE NONLYMPHOCYTIC LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; CHRONIC LYMPHOCYTIC-LEUKEMIA; SINGLE-NUCLEOTIDE POLYMORPHISMS; ORGANIC CATION TRANSPORTER-1; DOSE CYTOSINE-ARABINOSIDE; P-GLYCOPROTEIN; MULTIDRUG-RESISTANCE;
D O I
10.1016/j.blre.2015.08.001
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Acute myeloid leukemia is a clonal but heterogeneous disease differing in molecular pathogenesis, clinical features and response to chemotherapy. This latter frequently consists of a combination of cytarabine and anthracyclines, although etoposide, demethylating agents, and other drugs are also used. Unfortunately, chemoresistance is a common and serious problem. Multiple mechanisms account for impaired effectiveness of drugs and reduced levels of active agents in target cells. The latter can be due to lower drug uptake, increased export or decreased intracellular proportion of active/inactive agent due to changes in the expression/function of enzymes responsible for the activation of pro-drugs and the inactivation of active agents. Characterization of the "resistome", or profile of expressed genes accounting for multi-drug resistance (MDR) phenotype, would permit to predict the lack of response to chemotherapy and would help in the selection of the best pharmacological regime for each patient and moment, and to develop strategies of chemosensitization. (C) 2015 Elsevier Ltd. All rights reserved.
引用
收藏
页码:55 / 64
页数:10
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