Induction of ferroptosis for cancer therapy
OwnerXuejun Jiang, Craig B. Thompson +2inventors
InventorsXuejun Jiang, Craig B. Thompson, Jiajun Zhu, Junmei Yi
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Abstract
The present invention provides methods for the treatment of cancers by administration of inhibitors of the PI3K-AKT-mTORCl pathway (or components downstream of this pathway such as SREBP and SCD1) and agents that induce ferroptosis to subjects in need thereof. The present invention also provides various related compositions and related methods.
Claims45
A method of treating a tumor in a mammalian subject in need thereof, the method comprising administering to the subject an effective amount of both (a) an inhibitor of the PI3K/Akt/MTOR signaling axis and (b) an inducer of ferroptosis, thereby reducing the growth of and/or causing regression of the tumor in the subject.
The method of any of the preceding claims, wherein the subject has a breast tumor.
The method of any of the preceding claims, wherein the inhibitor of the PI3K/Akt/MTOR signaling axis is selected from the group consisting of a PI3K inhibitor, an Akt inhibitor, an MTOR inhibitor, an MTORC1 inhibitor, an SREBP inhibitor and SCD1 inhibitor.
The method of any of the preceding claims, wherein the inhibitor of the PI3K/Akt/MTOR signaling axis is a PI3K inhibitor.
The method of any of the preceding claims, wherein the inducer of ferroptosis is selected from the group consisting of RSL3, erastin, imidazole ketone erastin (IKE), sulfasalazine, sorafenib, altretamine, artesunate, ML-162 and ML-210.
A therapeutic composition comprising:
- (a) an inhibitor of the PI3K/Akt/MTOR signaling axis, (b) an inducer of ferroptosis and (c) a therapeutically acceptable carrier, for use in treatment of a tumor in a subject in need thereof.
The combination of (a) an inhibitor of the PI3K/Akt/MTOR signaling axis and (b) an inducer of ferroptosis, for use in treatment of a tumor in a subject in need thereof.
Dependencies are inferred from the claim text.