The full Chinese name for FLT3 is FMS-like tyrosine kinase 3, a type of tyrosine kinase, which is a class of enzymes that transfer phosphate groups to protein tyrosines. Excessive activation of intracellular tyrosine kinase activity results in altered biological behavior of cell proliferation, differentiation, and apoptosis.
The development and progression of many cancers are now thought to be closely related to tyrosine kinases. aberrant activation of FLT3 is closely associated with the development of many tumors, especially acute myeloblastic leukemia (AML). mutations in the FLT3 gene are the most common mutations in patients with AML, and mutations in the FLT3-ITD gene are the Patients with AML with FLT3 gene mutations have a poor prognosis because of poor chemotherapeutic efficacy, susceptibility to drug resistance, and a high risk of relapse even after bone marrow transplantation.
Common FLT3 inhibitors include:
- Midostaurin: In 2017, the FLT3 inhibitor midostaurin was formally approved by the FDA for use in combination with conventional chemotherapy for newly diagnosed FLT3 positive AML primary patients, the first targeted therapy to be used in combination with chemotherapy for AML. This is the first targeted therapy to be used in combination with chemotherapy for AML and the first major breakthrough in leukemia treatment in 25 years.
- Ponatinib (or ponatinib, Ponatinib): In 2009, the FDA approved ponatinib for the treatment of chronic myelogenous leukemia (CML) and Philadelphia chromosome-positive (Ph +) acute lymphoblastic leukemia (ALL), and its treatment in AML is still in clinical trials.
- Quizartinib: Quizartinib inhibits FLT3-ITD type AML well and is the most potent and selective FLT3 inhibitor available, with good selectivity and fewer side effects compared to midostaurin. Quizartinib also has a longer half-life in vivo and a greater ability to sustain FLT3 inhibition. Therefore, Quizartinib is more effective in patients with refractory/recurrent AML.
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Newer FLT3 inhibitors, such as Crenolanib and Gilteritinib, are still in clinical trials these days.
Dr. Xiao Dan of the Department of Hematology at Shanghai Renji Hospital South Hospital also contributed to this article