Cellular and pharmacologic aspects of drug resistance in acute myeloid leukemia.
Modern treatments and supportive care regimens for acute myeloid leukemia have produced some cures of what was once a uniformly fatal disease. To enhance the cure rate, intense efforts are now being put forth to understand the mechanisms of resistance to chemotherapeutic regimens that actually arise in clinical cases of acute myeloid leukemia, and to develop ways and means to circumvent such resistance. This review focuses on such efforts involving daunorubicin and cytarabine, the two most effective agents currently available for treatment of the disease. Most current published studies of daunorubicin have focused on detecting the classic form of multidrug resistance. For cytarabine, pharmacologically directed treatment approaches and enhancement of cytarabine leukemic cell kill by increasing the distribution of cells in S-phase and manipulating cellular cytarabine transport are currently under investigation.
Ross
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University of Maryland Cancer Center, Baltimore.
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D001692:Biological Transport; D003561:Cytarabine / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D004273:DNA, Neoplasm / Q000032:analysis; D003630:Daunorubicin / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D004351:Drug Resistance; D005784:Gene Amplification; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008562:Membrane Glycoproteins / Q000235:genetics; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism; D012189:Retrospective Studies
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D008562:Membrane Glycoproteins; D003561:Cytarabine; D003630:Daunorubicin