FLT3 Tyrosine Kinase Inhibition as a Paradigm for Targeted Drug Development in Acute Myeloid Leukemia

Therapy targeting specific somatic mutations has become an increasingly important part of cancer therapy over the past 20 years. In particular, tyrosine kinase inhibitors (TKIs) have become a critical component of treatment for both solid tumors and hematologic malignancies. Since mutations in the FMS-like tyrosine kinase 3 (FLT3) gene are relatively common in acute myeloid leukemia (AML), activating mutations in FLT3 represent an appealing target for drug development. Efforts are well underway to develop FLT3 inhibitors and to incorporate these agents into AML therapy. As the genetic landscape of AML has been mapped, other attractive targets for therapy have been discovered, including C-KIT, IDH1 and IDH2, NPM1, and MEK. Some lessons from the ongoing endeavor to develop FLT3 inhibitors may be applicable to the development of other targeted agents for AML.