Methods for the treatment of cancer

Abstract

The present invention is directed to methods for treating cancer in a subject, such as a cancer of the endocrine system. In some aspects, the method includes administering to the subject one or more of a polo-like kinase 1 inhibitor, a mouse double minute 2 inhibitor, and/or a mitotic catastrophe inducing compound. In other aspects, the method includes measuring an expression level of one or more markers, including caspase 8 and caspase 9, to assess the functionality of the caspase cascade in the subject.

What is claimed is: 
     
         1 . A method of treating endocrine cancer in a subject, the method comprising the steps of:
 administering a therapeutically effective amount of a polo-like kinase 1 Inhibitor (PLK1 inhibitor) to the subject; and   administering a therapeutically effective amount of a mouse double minute 2 inhibitor (MDM2 inhibitor) to the subject.   
     
     
         2 . The method of  claim 1 , wherein the endocrine cancer is a cancer of an adrenal gland. 
     
     
         3 . The method of  claim 1 , wherein the endocrine cancer is a malignant cancer of the adrenal gland. 
     
     
         4 . The method of  claim 3 , wherein the malignant cancer of the adrenal gland is adrenocortical carcinoma. 
     
     
         5 . The method of  claim 1 , wherein the PLK1 inhibitor is selected from the group consisting of BI-2536, cyclapolin 9, GW 843682X, TC-S 7005, Wortmannin, NMS-P937, and GSK461364A. 
     
     
         6 . The method of  claim 5 , wherein the PLK1 inhibitor is BI-2536. 
     
     
         7 . The method of  claim 1 , wherein the MDM2 inhibitor is selected from the group consisting of nutlin, caylin-1, HU 373, caylin-2, JNJ 26854165, NSC 66811, and trans-4-Indo, 4′-boranyl-chalcone. 
     
     
         8 . The method of  claim 7 , wherein the nutlin is nutlin-3. 
     
     
         9 . The method of  claim 1 , wherein the MDM2 inhibitor and the PLK1 inhibitor are administered as a single pharmaceutical composition. 
     
     
         10 . The method of  claim 1 , wherein the MDM2 inhibitor and the PLK1 inhibitor are administered as individual doses. 
     
     
         11 . A method of treating a subject with a caspase cascade defect, the method comprising the steps of:
 administering a therapeutically effective amount of a polo-like kinase 1 Inhibitor (PLK1 inhibitor) to the subject; and   administering a therapeutically effective amount of a mouse double minute 2 inhibitor (MDM2 inhibitor) to the subject.   
     
     
         12 . The method of  claim 11 , wherein the PLK1 inhibitor is selected from the group consisting of BI-2536, cyclapolin 9, GW 843682X, TC-S 7005, Wortmannin, NMS-P937, and GSK461364A. 
     
     
         13 . The method of  claim 12 , wherein the PLK1 inhibitor is BI-2536. 
     
     
         14 . The method of  claim 11 , wherein the MDM2 inhibitor is selected from the group consisting of nutlin, caylin-1, HU 373, caylin-2, JNJ 26854165, NSC 66811, and trans-4-Indo, 4′-boranyl-chalcone. 
     
     
         15 . The method of  claim 14 , wherein the MDM2 inhibitor is nutlin-3. 
     
     
         16 . The method of  claim 11 , wherein the MDM2 inhibitor and the PLK1 inhibitor are administered as a single pharmaceutical composition. 
     
     
         17 . A method of treating endocrine cancer in a subject, the method comprising the steps of:
 identifying a caspase cascade defect in the subject; and   administering a therapeutically effective amount of mitotic catastrophe inducing composition to the subject, wherein the mitotic catastrophe inducing composition comprises a PLK1 inhibitor and an MDM2 inhibitor.   
     
     
         18 . The method of  claim 17 , wherein the endocrine cancer is a cancer of the adrenal gland. 
     
     
         19 . The method of  claim 17 , wherein the identifying a caspase cascade defect comprises identifying an expression level of at least one marker. 
     
     
         20 . The method of  claim 19 , wherein the at least one marker is selected from the group consisting of caspase 8, caspase 9, and p53.