The Development of FLT3 Inhibitors in Acute Myeloid Leukemia

Hematol Oncol Clin North Am. 2017 Aug;31(4):663-680. doi: 10.1016/j.hoc.2017.03.002. Epub 2017 May 17.

Abstract

FLT3 mutations, generally associated with a poor prognosis, are found in approximately one-third of patients with acute myeloid leukemia (AML) and represent an attractive therapeutic target. FLT3 inhibitors undergoing clinical evaluation include first-generation relatively non-specific small molecules and second-generation compounds with higher potency and selectivity against mutant FLT3. Recently presented results from a prospective randomized clinical trial will likely lead to a change in the standard of care for younger patients with FLT3-mutated AML: addition of the multi-targeted FLT3 inhibitor midostaurin to standard induction and consolidation chemotherapy. Thus, personalized therapies for this subset of AML will soon be possible.

Keywords: AML; FLT3 inhibitors; FLT3 mutation; FLT3-ITD; FLT3-TKD.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Clinical Trials as Topic
  • Drug Discovery*
  • Drug Resistance, Neoplasm
  • Humans
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / genetics
  • Leukemia, Myeloid, Acute / metabolism*
  • Leukemia, Myeloid, Acute / mortality
  • Mutation
  • Prognosis
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use*
  • Recurrence
  • Signal Transduction / drug effects
  • Treatment Outcome
  • fms-Like Tyrosine Kinase 3 / antagonists & inhibitors*
  • fms-Like Tyrosine Kinase 3 / genetics
  • fms-Like Tyrosine Kinase 3 / metabolism

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • fms-Like Tyrosine Kinase 3