FLT3 signaling and the development of inhibitors that target FLT3 kinase activity

Abstract

The FMS-like receptor tyrosine kinase-3 (FLT3) plays a key role in hematopoietic development and is frequently mutated in patients with acute myeloid leukemia (AML). These mutations render FLT3 constitutively active, and patients harboring these mutations have a poor prognosis. Targeting the kinase activity of FLT3 with inhibitory compounds is therefore an attractive therapeutic option. Over the last few years, numerous FLT3 inhibitors have undergone clinical trials. Although some have been disappointing, some newer agents have shown promise. This review provides an overview of FLT3 signaling, recent progress with next-generation inhibitors, and unexpected hurdles encountered when combining FLT3 inhibitors with chemotherapy.