New agents in acute myeloid leukemia: beyond cytarabine and anthracyclines.
The standard therapeutic approaches for acute myeloid leukemia (AML) continue to be based on anthracyclines and cytarabine. However, the prognosis for AML remains poor, especially for patients with high-risk disease. During the past decade, promising novel agents that target DNA replication and repair, as well as cell cycling and apoptosis, have been developed and are being actively investigated in AML. Among these agents is flavopiridol, which interferes with key steps of the cell cycle and effectively promotes cell death, and voreloxin, an intercalating agent that also targets topoisomerase II. Also under clinical study in AML are oligonucleotide antisense constructs, which suppress the translation of proteins essential for leukemic blast survival and proliferation, and agents that target antiapoptotic cascades. In summary, it is hoped that novel therapies such as these will augment and/or supplant our current cytarabine- and anthracycline-based approaches, overcome active drug-resistance pathways, and eventually improve outcomes for patients with AML.
Fathi
Amir T
AT
Division of Hematologic Malignancies, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, 1650 Orleans Street, CRB 1 Room 289, Baltimore, MD 21231, USA.
Karp
Judith E
JE
D000208:Acute Disease; D018943:Anthracyclines / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects*; D003561:Cytarabine / Q000627:therapeutic use; D005419:Flavonoids / Q000627:therapeutic use; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000473:pathology; D010880:Piperidines / Q000627:therapeutic use
D018943:Anthracyclines; D000970:Antineoplastic Agents; D005419:Flavonoids; D010880:Piperidines; D003561:Cytarabine; C077990:alvocidib
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