Compositions and methods for treating cancer
The invention provides compositions and methods to treat a hyperproliferative disorder with a GSH synthesis inhibitor and an anti-cancer composition.
1. A combination of a glutathione (GSH) synthesis inhibitor and an anti-cancer composition comprising vemurafenib, whereby the GSH synthesis inhibitor is included in a dosage of from 1.5-17 g/m 2 buthionine sulphoximine (BSO).
2. The combination of claim 1 , wherein the GSH synthesis inhibitor is administered simultaneously with the anti-cancer composition.
3. The combination of claim 1 , wherein the GSH synthesis inhibitor and the anti-cancer composition are administered sequentially.
4. The combination of claim 1 , wherein administration of the anti-cancer composition begins about 1 to about 10 days before administration of the GSH synthesis inhibitor.
5. The combination of claim 1 , wherein administration of the GSH synthesis inhibitor begins about 1 to about 10 days before administration of the anti-cancer composition.
6. The combination of claim 1 , wherein administration of the GSH synthesis inhibitor and administration of the anti-cancer composition begin on the same day.
7. The combination of claim 1 , wherein the anti-cancer composition further comprises cobimetinib.
8. The combination of claim 1 , wherein the anti-cancer composition comprises a derivative of triphenylphosphonium (TPP).
9. The combination of claim 1 , wherein the anti-cancer composition comprises ipilimumab.
10. A kit comprising a GSH synthesis inhibitor, a container, and a package insert or label indicating the administration of the GSH synthesis inhibitor with an anti-cancer composition for treating melanoma, whereby the GSH synthesis inhibitor is buthionine sulphoximine (BSO) in a dosage of from 1.5-17 g/m 2 , and further providing that the anti-cancer composition comprises vemurafenib.
11. A method for treating a drug-resistant melanoma in a mammal, comprising administering to the mammal that is resistant to MAPK pathway inhibitor and/or could acquire resistance to MAPK pathway inhibitors a combination of a GSH synthesis inhibitor and vemurafenib, whereby the GSH synthesis inhibitor and the vemurafenib are administered sequentially, and further providing that the GSH synthesis inhibitor comprises buthionine sulphoximine (BSO) in a dosage of from 1.5-17 g/m 2 .
12. The method of claim 11 whereby the BSO is administered 1-10 days prior to the vemurafenib.
13. The method of claim 11 whereby the vemurafenib is administered 1-10 days prior to the BSO.
14. A method for treating a drug-resistant melanoma in a mammal, comprising administering to the mammal that is resistant to MAPK pathway inhibitor and/or could acquire resistance to MAPK pathway inhibitors a combination of buthionine sulphoximine (BSO) and vemurafenib, and further providing that the BSO is administered in a dosage of from 1.5-17 g/m2.