title: Role of drug transport and metabolism in the chemoresistance of acute myeloid leukemia.
abstract: 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.
authors: Laboratory of Experimental Hepatology and Drug Targeting (HEVEFARM), IBSAL, National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd), University of Salamanca, Salamanca, Spain.
authors: Jose J G
authors: JJ
authors: Marin
authors: Laboratory of Experimental Hepatology and Drug Targeting (HEVEFARM), IBSAL, National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd), University of Salamanca, Salamanca, Spain.
authors: Oscar
authors: O
authors: Briz
authors: Department of Hematology-BMT Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors: Gabriela
authors: G
authors: Rodríguez-Macias
authors: Department of Hematology-BMT Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Gregorio Marañon Institute for Health Research (IISGM), Madrid, Spain.
authors: José L
authors: JL
authors: Díez-Martín
authors: Laboratory of Experimental Hepatology and Drug Targeting (HEVEFARM), IBSAL, National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd), University of Salamanca, Salamanca, Spain. Electronic address: rociorm@usal.es.
authors: Rocio I R
authors: RI
authors: Macias
mesh_terms: D018943:Anthracyclines / Q000493:pharmacokinetics / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001692:Biological Transport; D054316:Biomarkers, Pharmacological / Q000378:metabolism; D001711:Biotransformation; D003561:Cytarabine / Q000493:pharmacokinetics / Q000627:therapeutic use; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005047:Etoposide / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D057285:Precision Medicine; D011355:Prodrugs / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D018943:Anthracyclines; D054316:Biomarkers, Pharmacological; D011355:Prodrugs; D003561:Cytarabine; D005047:Etoposide
keywords: Biotransformation; Cancer; Chemotherapy; Drug efflux; Drug uptake