Tyrosine kinase inhibitors targeting FLT3 in the treatment of acute myeloid leukemia

Yun Chen, Yihang Pan, Yao Guo, Wanke Zhao, Wanting Tina Ho, Jianlong Wang, Mingjiang Xu, Feng-Chun Yang, Zhizhuang Joe Zhao

Research output: Contribution to journalReview article

10 Citations (Scopus)

Abstract

Acute myeloid leukemia (AML) is a cancer of the myeloid lineage of blood cells. Although significant progress has been made in treating many types of cancers during recent years, AML remains a deadly disease with survival rate lagging behind other blood cancers. A combination of toxic chemotherapies has been the standard AML treatment for more than 40 years. With intensive efforts to define the pathogenesis of AML, novel therapeutic drugs targeting key molecular defects in AML are being developed. Mutated in nearly 30% of AML, FMS-like tyrosine kinase 3 (FLT3) represents one of the most attractive targets. FLT3 mutants resulted from either internal tandem duplication (ITD) or point mutations possess enhanced kinase activity and cause constitutive activation of signaling. To date, several small molecule inhibitors of FLT3 have been developed but their clinical efficacy is limited due to a lack of potency and the generation of drug resistance. Therefore, next-generation FLT3 inhibitors overcoming these limitations are urgently in need. This review focuses on the pathological role of mutant FLT3 in the development of AML, the current status of FLT3 inhibitor development, and mechanisms underlining the development of resistance to existing FLT3 inhibitors.

Original languageEnglish (US)
Article number48
JournalStem Cell Investigation
Volume4
Issue number6
DOIs
StatePublished - Jun 1 2017

Fingerprint

Acute Myeloid Leukemia
Protein-Tyrosine Kinases
Therapeutics
Neoplasms
Poisons
Drug Delivery Systems
Combination Drug Therapy
Point Mutation
Drug Resistance
Blood Cells
Phosphotransferases

Keywords

  • FMS-like tyrosine kinase 3 (FLT3)
  • Leukemia
  • Tyrosine kinase inhibitors (TKIs)

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology
  • Genetics
  • Developmental Biology

Cite this

Chen, Y., Pan, Y., Guo, Y., Zhao, W., Ho, W. T., Wang, J., ... Zhao, Z. J. (2017). Tyrosine kinase inhibitors targeting FLT3 in the treatment of acute myeloid leukemia. Stem Cell Investigation, 4(6), [48]. https://doi.org/10.21037/sci.2017.05.04

Tyrosine kinase inhibitors targeting FLT3 in the treatment of acute myeloid leukemia. / Chen, Yun; Pan, Yihang; Guo, Yao; Zhao, Wanke; Ho, Wanting Tina; Wang, Jianlong; Xu, Mingjiang; Yang, Feng-Chun; Zhao, Zhizhuang Joe.

In: Stem Cell Investigation, Vol. 4, No. 6, 48, 01.06.2017.

Research output: Contribution to journalReview article

Chen, Yun ; Pan, Yihang ; Guo, Yao ; Zhao, Wanke ; Ho, Wanting Tina ; Wang, Jianlong ; Xu, Mingjiang ; Yang, Feng-Chun ; Zhao, Zhizhuang Joe. / Tyrosine kinase inhibitors targeting FLT3 in the treatment of acute myeloid leukemia. In: Stem Cell Investigation. 2017 ; Vol. 4, No. 6.
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