Regorafenib promotes ferroptosis in acute myeloid leukemia by upregulating NOX4.

Acute Myeloid Leukemia (AML) is a challenging hematologic malignancy with limited long-term survival rates. This study explored the role of Regorafenib in promoting ferroptosis in AML cells through modulation of NOX4 expression. We demonstrated that Regorafenib sensitizes AML cells to ferroptosis induction both in vitro and in vivo. Mechanistically, Regorafenib treatment upregulated the expression of the NOX4 protein, leading to increased lipid peroxidation. Consistently, NOX4 inhibitor significantly rescued the ferroptosis promoting effect of Regorafenib. Importantly, combining Regorafenib with ferroptosis inducers showed synergistic effect of blocking tumor growth in vivo. This study highlights the potential of Regorafenib as an agent that modulates NOX4 expression, offering new insights into the treatment of AML.