By Melissa Badamo - Last Updated: February 8, 2024
Foretinib effectively inhibited FLT3 and promoted apoptosis in acute myeloid leukemia (AML) cell lines by directly binding to FLT3, according to a study published in Cancer Research.
The novel tyrosine kinase inhibitor also showed potent activity against secondary mutations that drive resistance to quizartinib and gilteritinib.
The researchers conducted a virtual library screening of about 60,000 small molecules and identified foretinib as a potent FLT3 inhibitor. Compared with the FLT3 inhibitors gilteritinib, quizartinib, midostauin, and sorafenib, foretinib exhibited stronger efficacy in inhibiting FLT3– internal tandem duplication (ITD) cell growth and treating FLT3-ITD AML.
Foretinib also extended the survival of mice with cell- and patient-derived FLT3-ITD xenografts. NOD scid gamma (NSG) mice were injected with MOLM13 or MV4-11 cells then randomly administered either foretinib, gilteritinib, quizartinib, or a control treatment. In the MOLM13 mice model, leukemia cells made up 0.07% of cells in the foretinib group, 13.8% of cells in the giltertinib group, 2.13% of cells in the quizartinib group, and 74.6% of cells in the control group.
“These findings support the potential of foretinib for treating AML patients with FLT3-ITD mutations, especially for those carrying secondary mutations after treatment failure with other FLT3 inhibitors,” the researchers concluded.
Reference
Wang P, Zhang Y, Xiang R, et al. Foretinib is effective in acute myeloid leukemia by inhibiting FLT3 and overcoming secondary mutations that drive resistance to quizartinib and gilteritinib. Cancer Res. 2024. doi:10.1158/0008-5472.CAN-23-1534
Original Source: Foretinib Treatment Inhibits FLT3, Effective in AML Cell Lines | Blood Cancers Today