Metakaryocidal Treatments

Abstract

The invention provides, inter alia, methods of treating a disorder characterized by excessive metakaryotic stem cell growth by a combination metakaryocidal therapy. Also encompassed by the present invention are preventative methods comprising the administration of a metakaryocidal or metakayrostatic therapeutic agent.

What is claimed is: 
     
         1 . A method of treating a disorder characterized by excessive metakaryotic stem cell growth in a mammalian subject in need thereof comprising providing a therapeutically effective combination metakaryocidal therapy, in which exposure of the subject to each separate metakaryocidal drug is uninterrupted, thereby treating the disorder. 
     
     
         2 . The method of  claim 1 , wherein the subject receives concurrent or sequential eukaryocidal treatment. 
     
     
         3 . A method of treating a disorder characterized by excessive metakaryotic stem cell growth in a mammalian subject in need thereof comprising sequential eukaryocidal treatment. 
     
     
         4 . The method of  claim 1 , wherein the combination metakaryocidal therapy comprises concurrent or sequential administration of three or more metakaryocidal treatments. 
     
     
         5 . The method of  claim 4 , wherein the combination metakaryocidal therapy comprises concurrent or sequential administration of four or more metakaryocidal treatments. 
     
     
         6 . The method of  claim 5  wherein the combination metakaryocidal therapy comprises concurrent or sequential administration of five or more metakaryocidal treatments. 
     
     
         7 . The method of  claim 6 , wherein the combination metakaryocidal therapy comprises concurrent or sequential administration of six or more metakaryocidal treatments. 
     
     
         8 . The method of  claim 1 , wherein the combination metakaryocidal therapy comprises administering two or more metakaryocidal agents so as to achieve plasma concentrations of the agents for an uninterrupted duration substantially similar to the in vitro metakaryocidal concentrations and uninterrupted durations of the agents found to be metakaryocidal in HT-29 or CAPAN-1 cells. 
     
     
         9 . The method of  claim 1 , wherein the combination metakaryocidal therapy comprises administering an effective amount of three or more of captopril, celecoxib, doxycycline, metformin, verapamil, or acetaminophen. 
     
     
         10 . The method of  claim 1 , wherein the combination metakaryocidal therapy comprises administering an effective amount of four or more of captopril, celecoxib, doxycycline, metformin, or verapamil. 
     
     
         11 . The method of  claim 1 , wherein the combination metakaryocidal therapy comprises administering an effective amount of captopril, celecoxib, doxycycline, metformin, and verapamil. 
     
     
         12 . The method of  claim 11 , where the effective amount of captopril achieves a plasma concentration of about 0.125 to about 0.5 μM (e.g., about 0.25 μM), the effective amount of celecoxib achieves a plasma concentration of about 12.5 to about 50 μM (e.g., about 25 μM), the effective amount of doxycycline achieves a plasma concentration of about 2.5 to about 10 μM (e.g., about 5 μM), the effective amount of metformin achieves a plasma concentration of about 200 to about 800 μM (e.g., about 400 μM), and the effective amount of verapamil achieves a plasma concentration of about 2 to about 8 μM (e.g., about 4.0 μM). 
     
     
         13 . The method of  claim 1 , wherein the metakaryocidal treatments of the combination metakaryocidal therapy are each administered for a period of about 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or 13 weeks. 
     
     
         14 . The method of  claim 13 , wherein the metakaryocidal treatments of the combination metakaryocidal therapy are each administered for a period of about 3-7 weeks. 
     
     
         15 . The method of  claim 1 , wherein the metakaryocidal treatments of the combination metakaryocidal therapy are administered sequentially. 
     
     
         16 . The method of  claim 1 , wherein the disorder characterized by excessive metakaryotic stem cell growth is cancer. 
     
     
         17 . The method of  claim 16 , wherein the cancer is pancreatic cancer. 
     
     
         18 . The method of  claim 17 , wherein the subject undergoes the Whipple procedure before, after, or during the combination metakaryocidal therapy. 
     
     
         19 . The method of  claim 1 , wherein the plasma concentration of each metakaryocidal agent in the combination therapy is maintained substantially constant. 
     
     
         20 . The method of  claim 1 , wherein there is a resting interval between the administration of each separate metakaryocidal drug.