Methods for inducing ferroptosis in cancer
AssigneeBoard of Regents, The University of Texas System
InventorsBoyi Gan, Yuelong Yan
Life of this patent
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Abstract
The present disclosure provides methods for treating cancer using ferroptosis inducers in combination with one-carbon metabolism inhibitors. The combination of ferroptosis inducers and one-carbon metabolism inhibitors induce greater ferroptosis than treatment with either alone. In certain embodiments, the one-carbon metabolism inhibitors are serine hydroxymethyltransferase (SHMT) inhibitors and/or methylenetetrahydrofolate dehydrogenase (MTHFD) inhibitors. By way of example, the ferroptosis inducers are GPX4 inhibitors.
Claims23
A method of treating cancer in a subject comprising administering to the subject:
- a) one or more one-carbon metabolism inhibitors;
- and
- b) one or more ferroptosis inducers;
- wherein at least one one-carbon metabolism inhibitor is a serine hydroxymethyltransferase (SHMT) inhibitor, a methylenetetrahydrofolate dehydrogenase (MTHFD) inhibitor or a combination thereof, thereby treating cancer in the subject.
A method of enhancing ferroptosis in a tumor comprising exposing the tumor to:
- (a) one or more one-carbon metabolism inhibitors;
- and
- (b) one or more ferroptosis inducers,
- wherein the ferroptosis induced in the tumor is greater than the ferroptosis induced when the tumor is exposed to one or more ferroptosis inducers or one or more one-carbon metabolism inhibitors alone, and
- wherein at least one one-carbon metabolism inhibitor is a serine hydroxymethyltransferase (SHMT) inhibitor, a methylenetetrahydrofolate dehydrogenase (MTHFD) inhibitor or a combination thereof, thereby enhancing ferroptosis in the tumor.
A method of sensitizing cancer cells to ferroptosis comprising exposing the cancer cells to one or more one-carbon metabolism inhibitors,
- wherein at least one one-carbon metabolism inhibitor is a serine hydroxymethyltransferase (SHMT) inhibitor, a methylenetetrahydrofolate dehydrogenase (MTHFD) inhibitor or a combination thereof, thereby sensitizing the cancer cells to ferroptosis.
A pharmaceutical composition comprising:
- a) one or more one-carbon metabolism inhibitors;
- b) one or more ferroptosis inducers;
- and
- c) a pharmaceutically acceptable carrier.
Dependencies are inferred from the claim text.