Efficacy and Synergy of Small Molecule Inhibitors Targeting <i>FLT3</i>-ITD⁺ Acute Myeloid Leukemia.

ABSTRACT: Constitutive activation of FLT3 by ITD mutations is one of the most common genetic aberrations in AML, present in ~1/3 of cases. Patients harboring FLT3-ITD display worse clinical outcomes. The integration and advancement of FLT3 TKI in AML treatment provided significant therapeutic improvement. However, due to the emergence of resistance mechanisms, FLT3-ITD⁺ AML remains a clinical challenge. We performed an unbiased drug screen to identify 18 compounds as particularly efficacious against FLT3-ITD⁺ AML. Among these, we characterized two investigational compounds, WS6 and ispinesib, and two approved drugs, ponatinib and cabozantinib, in depth. We found that WS6, although not yet investigated in oncology, shows a similar mechanism and potency as po

SUBMITTER: Bregante J 

PROVIDER: S-EPMC8699584 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature