Bench to bedside targeting of FLT3 in acute leukemia

Curr Drug Targets. 2010 Jul;11(7):781-9. doi: 10.2174/138945010791320782.

Abstract

FMS-Like-Tyrosine kinase-3 (FLT3) mutations are found in about 30% of cases of acute myeloid leukemia and confer an increased relapse rate and reduced overall survival. Targeting this tyrosine kinase by direction inhibition is the focus of both preclinical and clinical research in AML. Several molecules are in clinical development inhibit FLT3, but thus far clinical responses have been limited. Correlative studies from monotherapy trials have established that responses require sustained, effective FLT3 inhibition in vivo. Studies combining FLT3 inhibitors with chemotherapy have demonstrated increased remission rates to date but have yet to produce a survival advantage. Currently the only approved FLT3 inhibitor available for off-label use is sorafenib, which clearly has clinical activity but does not commonly lead to a complete response. Several FLT3 inhibitors are currently being tested as single agents and in combination with chemotherapy, and it seems likely that a clinically useful drug will eventually emerge.

Publication types

  • Review

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biological Assay / methods
  • Drug Delivery Systems / methods
  • Drug Resistance, Neoplasm / genetics
  • Drugs, Investigational / pharmacology
  • Drugs, Investigational / therapeutic use
  • Humans
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / genetics
  • Mutation
  • Protein Kinase Inhibitors / pharmacology*
  • Protein Kinase Inhibitors / therapeutic use*
  • Translational Medical Research / methods*
  • fms-Like Tyrosine Kinase 3 / antagonists & inhibitors*
  • fms-Like Tyrosine Kinase 3 / genetics

Substances

  • Drugs, Investigational
  • Protein Kinase Inhibitors
  • FLT3 protein, human
  • fms-Like Tyrosine Kinase 3