Inhibition of FLT3 in AML: a focus on sorafenib.

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Antar A, Otrock ZK, El-Cheikh J, Kharfan-Dabaja MA, Battipaglia G, Mahfouz R, Mohty M, Bazarbachi A

Inhibition of FLT3 in AML: a focus on sorafenib.

Bone Marrow Transplant. 2017 Mar;52(3):344-351. doi: 10.1038/bmt.2016.251. Epub 2016 Oct 24.

PubMed ID

27775694 [ View in PubMed

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Abstract

FMS-like tyrosine kinase 3 (FLT3) is one of the most commonly mutated genes in AML. FLT3 is mutated in ~30% of patients with AML, either by internal tandem duplications (FLT3-ITD) of the juxta-membrane domain or by a point mutation, usually involving the tyrosine kinase domain. Several FLT3 tyrosine kinase inhibitors are being evaluated in multiple studies aiming at improving outcomes. The most widely used is sorafenib, a potent multikinase inhibitor approved for hepatocellular carcinoma and renal cell carcinoma. Sorafenib monotherapy or in combination with conventional chemotherapy, has been evaluated in various settings in AML, including front-line, relapsed or refractory disease including post-allograft failures and, more recently, as post-transplant maintenance therapy. Encouraging data have emerged with several other agents like lestaurtinib, midostaurin, crenolanib, gilteritinib and quizartinib. Although transient responses to FLT3 inhibitors are often observed in case of disease relapse, the most promising approach is the use of FLT3 inhibitors either in combination with induction chemotherapy or as consolidation/maintenance therapy after allogeneic hematopoietic cell transplantation. In this review, we summarize the clinical data on sorafenib and other FLT3 inhibitors in AML.

DrugBank Data that Cites this Article

Drugs

Gilteritinib

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Gilteritinib	ALK tyrosine kinase receptor	Protein	Humans	Yes	Inhibitor	Details
Gilteritinib	Receptor-type tyrosine-protein kinase FLT3	Protein	Humans	Yes	Inhibitor	Details
Gilteritinib	Tyrosine-protein kinase receptor UFO	Protein	Humans	Yes	Inhibitor	Details