Methods for treating glioblastoma
Described are methods for treating cancers, e.g., glioblastoma, including administering an inhibitor of Notch signalling, e.g., a gamma secretase inhibitor, in combination with a chemotherapeutic agent.
1. A method of treating glioblastoma in a subject, the method comprising:
selecting a subject who is in need of treatment for glioblastoma;
administering to the subject a therapeutically effective amount of temozolomide; and
administering to the subject a therapeutically effective amount of a gamma secretase inhibitor at least 24 hours after administering the temozolomide,
thereby treating the glioblastoma in the subject.
2. The method of claim 1 , wherein the gamma secretase inhibitor is selected from the group consisting of semagacestat; LY411575; N-[N-(3,5-difluorophenacetyl)-L-alanyl]-(S)-phenylglycine t-butyl ester (DAPT); Compound E; L-685,458; BMS-299897; MK0752; and MRK-003.
3. The method of claim 2 , wherein the gamma secretase inhibitor is LY411575.
4. The method of claim 1 , comprising administering two or more doses of the temozolomide.
5. The method of claim 1 , comprising administering two or more doses of the gamma secretase inhibitor.
6. The method of claim 2 , wherein the gamma secretase inhibitor is semagacestat.
7. The method of claim 2 , wherein the gamma secretase inhibitor is DAPT.
8. A method of treating glioblastoma in a subject, the method comprising:
selecting a subject who is in need of treatment for glioblastoma;
administering to the subject a therapeutically effective amount of temozolomide; and
administering to the subject a therapeutically effective amount of a gamma secretase inhibitor selected from the group consisting of semagacestat, LY411575, and N-[N-(3,5-difluorophenacetyl)-L-alanyl]-(S)-phenylglycine t-butyl ester (DAPT);
thereby treating the glioblastoma in the subject.
9. The method of claim 8 , wherein the gamma secretase inhibitor is administered after the temozolomide.
10. The method of claim 9 , wherein the gamma secretase inhibitor is administered at least 24 hours after administering the temozolomide.
11. The method of claim 8 , comprising administering two or more doses of the temozolomide.
12. The method of claim 8 , comprising administering two or more doses of the gamma secretase inhibitor.
13. The method of claim 8 , wherein the gamma secretase inhibitor is semagacestat.
14. The method of claim 8 , wherein the gamma secretase inhibitor is LY411575.
15. The method of claim 8 , wherein the gamma secretase inhibitor is DAPT.