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Validation of ITD mutations in FLT3 as a therapeutic target in human acute myeloid leukaemia
It is demonstrated that FLT3-ITD can represent a driver lesion and valid therapeutic target in human AML and AC220-resistant FLT 3 kinase domain mutants represent high-value targets for futureFLT3 inhibitor development efforts. Expand
AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML).
The data reveal that the combination of excellent potency, selectivity, and pharmacokinetic properties is unique to AC220, which therefore is the first drug candidate with a profile that matches the characteristics desirable for a clinical FLT3 inhibitor. Expand
Single-agent CEP-701, a novel FLT3 inhibitor, shows biologic and clinical activity in patients with relapsed or refractory acute myeloid leukemia.
Results show that FLT3 inhibition is associated with clinical activity in AML patients harboringFLT3-activating mutations and indicate that CEP-701 holds promise as a novel, molecularly targeted therapy for this disease. Expand
Phase I study of quizartinib administered daily to patients with relapsed or refractory acute myeloid leukemia irrespective of FMS-like tyrosine kinase 3-internal tandem duplication status.
Quizartinib has clinical activity in patients with relapsed/refractory AML, particularly those with FLT3-ITD, and is associated with an acceptable toxicity profile, and the dose-limiting toxicity was grade 3 QT prolongation. Expand
FLT3: ITDoes matter in leukemia
This review summarizes the data on the molecular biology and clinical impact ofFLT3 mutations, as well as the therapeutic potential of several small-molecule FLT3 inhibitors currently in development. Expand
A FLT3-targeted tyrosine kinase inhibitor is cytotoxic to leukemia cells in vitro and in vivo.
It is demonstrated that CEP-701 induces a cytotoxic effect on cells in a dose-responsive fashion that parallels the inhibition of FLT3, and form the basis for a planned clinical trial of the indolocarbazole derivative Cep-701 in patients with AML harboringFLT3- activating mutations. Expand
FLT3-mutant allelic burden and clinical status are predictive of response to FLT3 inhibitors in AML.
It is found that inhibition of FLT3 autophosphorylation in aFLT3/ITD specimen does not always induce cell death, suggesting that some patients with newly diagnosed FLT 3-mutant AML might be less likely to respond clinically to highly selective FLT2 inhibition. Expand
Results from a randomized trial of salvage chemotherapy followed by lestaurtinib for patients with FLT3 mutant AML in first relapse.
Overall, lestaurtinib treatment after chemotherapy did not increase response rates or prolong survival of patients withFLT3 mutant acute myeloid leukemia in first relapse, and any conclusions regarding the efficacy of combining FLT3 inhibition with chemotherapy are limited. Expand
A phase 2 trial of the FLT3 inhibitor lestaurtinib (CEP701) as first-line treatment for older patients with acute myeloid leukemia not considered fit for intensive chemotherapy.
Activating mutations of FMS-like tyrosine kinase 3 (FLT3) are present in approximately one third of patients with acute myeloid leukemia (AML) and are associated with adverse prognosis. The importantExpand
Targeting FLT3 mutations in AML: review of current knowledge and evidence
This review focuses on the pathological and prognostic role of FLT3 mutations in AML, clinical classification of the disease, recent progress with next-generationFLT3 inhibitors, and mechanisms of resistance to FLT 3 inhibitors. Expand