Methods for treating glioblastoma

Abstract

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.

What is claimed is: 
     
         1 . A method of treating a cellular proliferative disorder in a subject, the method comprising:
 selecting a subject who is in need of treatment for a cellular proliferative disorder;   administering to the subject a therapeutically effective amount of a chemotherapeutic agent; and   administering to the subject a therapeutically effective amount of a gamma secretase inhibitor,   thereby treating the cellular proliferative disorder in the subject.   
     
     
         2 . The method of  claim 1 , wherein the cellular proliferative disorder is glioblastoma. 
     
     
         3 . The method of  claim 1 , wherein the chemotherapeutic agent is an alkylating agent. 
     
     
         4 . The method of  claim 3 , wherein the alkylating agent is temozolomide (TMZ). 
     
     
         5 . The method of  claim 3 , wherein the alkylating agent is 1,3-Bis(2-chloroethyl)-1-nitrosourea (BCNU). 
     
     
         6 . The method of  claim 1 , wherein the gamma secretase inhibitor is selected from the group consisting of semagacestat; LY411575; Compound E; L-685,458; BMS-299897; MK0752; and MRK-003. 
     
     
         7 . The method of  claim 6 , wherein the gamma secretase inhibitor is LY411575. 
     
     
         8 . The method of  claim 1 , wherein the gamma secretase inhibitor is administered after the chemotherapeutic agent. 
     
     
         9 . The method of  claim 6 , wherein the gamma secretase inhibitor is administered at least 24 hours after the chemotherapeutic agent. 
     
     
         10 . The method of  claim 1 , comprising administering two or more doses of the chemotherapeutic agent. 
     
     
         11 . The method of  claim 1 , comprising administering two or more doses of the gamma secretase inhibitor. 
     
     
         12 . A kit comprising: one or more doses of a chemotherapeutic agent, and one or more doses of a gamma secretase inhibitor, and instructions for administration of the chemotherapeutic agent and the gamma secretase inhibitor. 
     
     
         13 . The kit of  claim 12 , comprising one or more doses of TMZ, and one or more doses of a gamma secretase inhibitor selected from the group consisting of semagacestat; LY411575; Compound E; L-685,458; BMS-299897; MK0752; and MRK-003.