Procaspase combination therapy for glioblastoma
The invention provides compositions and methods for the induction of cell death, for example, cancer cell death. Combinations of compounds and related methods of use are disclosed, including the use of compounds in therapy for the treatment of cancer and selective induction of apoptosis in cells. The disclosed drug combinations can have lower neurotoxicity effects than other compounds and combinations of compounds.
1. A method of treating cancer comprising administering to a subject in need of therapy for cancer of the brain, concurrently or sequentially, a therapeutically effective amount of a compound of Formula (I):
and a therapeutically effective amount of the compound PAC-1:
wherein the concentration of the compound of Formula I is about 250 μM to about 750 μM, and the concentration of PAC-1 is about 5 μM to about 30 μM, and apoptosis is induced in cells of the cancer of the brain and the cancer of the brain is thereby treated.
2. The method of claim 1 wherein the concentration of the compound of Formula I is 250 μM to 750 μM, and the concentration of PAC-1 is 5 μM to 30 μM.
3. The method of claim 1 wherein the compound of Formula (I) and the compound PAC-1 are administered by infusion, by injection, by oral administration, or a combination thereof.
4. The method of claim 1 wherein the compound of Formula (I) and the compound PAC-1 are administered orally.
5. The method of claim 1 wherein the compound of Formula (I) and the compound PAC-1 are administered concurrently.
6. The method of claim 1 wherein the compound of Formula (I) and the compound PAC-1 are administered sequentially, wherein the compound of Formula (I) is administered before the compound PAC-1, or the compound of Formula (I) is administered after the compound PAC-1.
7. A method of treating brain cancer consisting essentially of orally administering to a subject in need of brain cancer therapy, concurrently or sequentially, a therapeutically effective amount of a compound of Formula (I):
and a therapeutically effective amount of the compound PAC-1:
wherein the concentration of the compound of Formula I is about 250 μM to about 750 μM, and the concentration of PAC-1 is about 5 μM to about 30 μM, and apoptosis is induced in cells of the cancer of the brain and the cancer of the brain is thereby treated.
8. The method of claim 7 wherein the concentration of the compound of Formula I is 250 μM to 750 μM and the concentration of PAC-1 is 5 μM to 25 μM.
9. The method of claim 1 wherein the concentration of the compound of Formula I with respect to the concentration of PAC-1 is synergistic.
10. The method of claim 7 wherein the concentration of the compound of Formula I and the concentration of PAC-1 are synergistic.