New drugs in acute myeloid leukemia.
The acute myeloid leukemias (AML) are often fatal disorders with a range of clinical, morphologic, cytogenetic, and molecular features and a consequent need for a diverse array of therapies. This need for tailored therapy for subsets of patients with AML is exemplified in those with acute promyelocytic leukemia, the subject of a separate article in this issue (Tallman and Nabhan). Unfortunately, we tend to examine novel agents in patients with very advanced disease, in which prior therapies have inevitably altered the tumor. Of a myriad of possible exciting novel agents, a few, including PS-341, Genasense (Genta, Berkeley Heights, NJ), decitabine, 5-azacytidine, clofarabine, and troxacitabine, are briefly reviewed with an emphasis on their mechanisms of action from a perspective that suggests possible synergistic therapeutic interventions. With the growing appreciation of the pivotal role of angiogenesis in AML, angiogenesis modulators are a good example of a core class of drugs upon which future noncytotoxic combinations may be built. Those agents targeting vascular endothelial growth factor are also briefly reviewed.
Giles
Francis J
FJ
Section of Developmental Therapeutics, Department of Leukemia, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Box 428, Houston, TX 77030, USA. frankgiles@aol.com
D000208:Acute Disease; D000227:Adenine Nucleotides; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001087:Arabinonucleosides / Q000627:therapeutic use; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000068258:Bevacizumab; D001897:Boronic Acids / Q000627:therapeutic use; D000069286:Bortezomib; D000077866:Clofarabine; D003596:Cytosine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000077209:Decitabine; D004148:Dioxolanes / Q000627:therapeutic use; D006801:Humans; D007211:Indoles / Q000627:therapeutic use; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000473:pathology; D010793:Phthalazines / Q000627:therapeutic use; D011719:Pyrazines / Q000627:therapeutic use; D011725:Pyridines; D011758:Pyrroles / Q000627:therapeutic use; D013873:Thionucleotides / Q000627:therapeutic use
D000227:Adenine Nucleotides; D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D001087:Arabinonucleosides; D001897:Boronic Acids; D004148:Dioxolanes; D007211:Indoles; D010793:Phthalazines; D011719:Pyrazines; D011725:Pyridines; D011758:Pyrroles; D013873:Thionucleotides; D000068258:Bevacizumab; C404768:vatalanib; C074908:troxacitabine; D000069286:Bortezomib; C116890:Semaxinib; D000077866:Clofarabine; D000077209:Decitabine; C408162:oblimersen; D003596:Cytosine; D001374:Azacitidine