FLT3 inhibition as a targeted therapy for acute myeloid leukemia

The management of acute myeloid leukemia (AML) presents significant challenges, and there remains a need for new therapies with greater efficacy and better tolerability than existing treatments. An improved understanding of the genetic and molecular changes underlying AML can help both to guide treatment strategies and to predict clinical outcomes, thereby enabling more precise decision-making regarding the optimal treatment strategy for individual patients.

The tyrosine kinase receptor FLT3 plays an important role in the survival and proliferation of blasts, and approximately 25% of patients with AML have mutations in the FLT3 gene. This protein is therefore an obvious therapeutic target in AML. Amongst recently developed tyrosine kinase inhibitors of FLT3, lestaurtinib and midostaurin are two orally bioavailable agents that have shown encouraging activity, both preclinically and in relapsed AML, and are now in phase III clinical trials. These agents are also being tested in combination with conventional chemotherapy.

Oral FLT3 inhibitors offer a hope of improved treatment outcomes for patients with relapsed and newly diagnosed AML.