Novel therapeutic agents against cancer stem cells of chronic myeloid leukemia

Anticancer Agents Med Chem. 2010 Feb;10(2):111-5. doi: 10.2174/187152010790909326.

Abstract

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.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Arachidonate 15-Lipoxygenase / metabolism
  • Arachidonate 15-Lipoxygenase / physiology
  • Benzodiazepines / pharmacology
  • Benzodiazepines / therapeutic use
  • HSP90 Heat-Shock Proteins / antagonists & inhibitors
  • Harringtonines / pharmacology
  • Harringtonines / therapeutic use
  • Hedgehog Proteins / antagonists & inhibitors
  • Homoharringtonine
  • Humans
  • Imidazoles / pharmacology
  • Imidazoles / therapeutic use
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology
  • Lipoxygenase Inhibitors
  • Medical Oncology / trends
  • Mice
  • Models, Biological
  • Neoplastic Stem Cells / drug effects*
  • Neoplastic Stem Cells / pathology
  • Signal Transduction / drug effects

Substances

  • Antineoplastic Agents
  • HSP90 Heat-Shock Proteins
  • Harringtonines
  • Hedgehog Proteins
  • Imidazoles
  • Lipoxygenase Inhibitors
  • Benzodiazepines
  • Homoharringtonine
  • Arachidonate 15-Lipoxygenase
  • 7-cyano-2,3,4,5-tetrahydro-1-(1H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-(2-thienylsulfonyl)-1H-1,4-benzodiazepine