At the American Association for Cancer Research (AACR) annual meeting in Washington, DC, USA, on Monday 3rd April, a poster session titled “Growth Factor and Hormone Receptors as Therapeutic Targets” took place.
During this session, a poster (2094 /21) titled “Dual inhibition of FLT3 and Src pathways by ON150030, a type 1 inhibitor, as a novel strategy for relapsed and refractory AML therapy” by Helya Ghaffari and colleagues from the Icahn School of Medicine at Mount Sinai, New York City, was on display.
Quizartinib inhibits FLT3-ITD in Acute Myeloid Leukemia (AML). Quizartinib binds to the inactive form of FLT3 but fails to inhibit FLT3-ITD harboring D835 mutation. In this study, the authors investigated the efficacy of ON150030, a type 1 inhibitor, which binds to the active form of FLT3.
The key results were:
- Compared to quizartinib, ON150030 inhibited both wild-type and FLT3-D835Y
- ON150030 inhibited the growth of MV4-11 cells (FLT3-ITD positive AML cell line) harboring FLT3-ITD mutations
- Increasing dose of ON150030 in MV4-11 cells was associated with an inhibition of MAPK and PI3K/AKT pathways in these cells
- ON150030 reduces JAK independent phosphorylation of STAT5
In summary, ON15003 is a novel inhibitor with strong activity against SRC and FLT3 kinases. The authors highlighted that the distinct mode of action of ON15003 could be promising for therapy in AML.