Novel therapeutic agents against cancer stem cells of chronic myeloid leukemia.
Chronic myeloid leukemia (CML) is induced by the BCR-ABL oncogene, a product of Philadelphia (Ph) chromosome. The BCR-ABL kinase inhibitor imatinib is a standard treatment for Ph+ leukemia, and has been shown to induce a complete hematologic and cytogenetic response in most chronic phrase CML patients. However, imatinib does not cure CML, and one of the reasons is that imatinib does not kill leukemia stem cells (LSCs) in CML both in vitro and in vivo. Recently, several new targets or drugs have been reported to inhibit LSCs in cultured human CD34+ CML cells or in mouse model of BCR-ABL induced CML, including an Alox5 pathway inhibitor, Hsp90 inhibitors, omacetaxine, hedgehog inhibitor and BMS-214662. Specific targeting of LSCs but not normal stem cell is a correct strategy for developing new anti-cancer therapies in the future.
Chen
Yaoyu
Y
Division of Hematology/Oncology, Department of Medicine, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA.
Peng
Cong
C
Sullivan
Con
C
Li
Dongguang
D
Li
Shaoguang
S
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001093:Arachidonate 15-Lipoxygenase / Q000378:metabolism / Q000502:physiology; D001569:Benzodiazepines / Q000494:pharmacology / Q000627:therapeutic use; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors; D006248:Harringtonines / Q000494:pharmacology / Q000627:therapeutic use; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors; D000077863:Homoharringtonine; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000473:pathology; D016859:Lipoxygenase Inhibitors; D008495:Medical Oncology / Q000639:trends; D051379:Mice; D008954:Models, Biological; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects
D000970:Antineoplastic Agents; D018841:HSP90 Heat-Shock Proteins; D006248:Harringtonines; D053823:Hedgehog Proteins; D007093:Imidazoles; D016859:Lipoxygenase Inhibitors; D001569:Benzodiazepines; D000077863:Homoharringtonine; D001093:Arachidonate 15-Lipoxygenase; C415151:7-cyano-2,3,4,5-tetrahydro-1-(1H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-(2-thienylsulfonyl)-1H-1,4-benzodiazepine