Methods and products for treating proliferative diseases

Abstract

Methods and products for treating proliferative diseases, and wounds, using as a pharmacon an autophagy inhibitor, a glycolytic inhibitor, and/or an agent able to alter cellular production of reactive oxygen, or combination thereof, optionally in combination with one or more chemotherapeutic agents. In some embodiments, the invention combines a 4-aminoquinoline, exemplified by chloroquine, with a glycolytic inhibitor, exemplified by 2-deoxy-D-glucose and anti-VEGF antibodies. The systems and methods of the invention may be used to treat drug-resistant or multi-drug resistant cancers

What is claimed is: 
     
         1 . A method for treating melanoma, comprising:
 administering to a subject a therapeutically acceptable amount of an autophagy inhibitor and an anti-VEGF antibody in an effective amount to treat the melanoma.   
     
     
         2 . The method of  claim 1 , wherein the anti-VEGF antibody is bevacizumab. 
     
     
         3 . The method of  claim 1 , wherein the autophagy modulator is a 4-aminoquinoline. 
     
     
         4 . The method of  claim 3  wherein the 4-aminoquinoline is a chloroquine compound having the formula: 
       
         
           
           
               
               
           
         
       
     
     
         5 . The method of  claim 1 , wherein the autophagy inhibitor is chloroquine. 
     
     
         6 - 8 . (canceled) 
     
     
         9 . A method for treating a drug resistant tumor, comprising:
 administering to a subject a therapeutically acceptable amount of an autophagy inhibitor and a glycolytic inhibitor in an effective amount to treat the drug resistant tumor.   
     
     
         10 . The method of  claim 9 , wherein the drug resistant tumor is a melanoma. 
     
     
         11 . The method of  claim 9 , wherein the drug resistant tumor is an ovarian tumor. 
     
     
         12 . The method of  claim 9 , wherein the drug resistant tumor is a glioblastoma. 
     
     
         13 . The method of  claim 9 , further comprising administering an anticancer agent to the subject. 
     
     
         14 . The method of  claim 9 , further comprising administering a fatty acid metabolism inhibitor to the subject. 
     
     
         15 . A method for treating a drug sensitive tumor, comprising:
 administering to a subject a therapeutically acceptable amount of an autophagy inhibitor, a glycolytic inhibitor, and an anti-cancer agent in an effective amount to treat the drug sensitive tumor.   
     
     
         16 . The method of  claim 15 , wherein the drug sensitive tumor is a melanoma. 
     
     
         17 . The method of  claim 15 , wherein the drug sensitive tumor is an ovarian tumor. 
     
     
         18 . The method of  claim 15 , wherein the drug sensitive tumor is a glioblastoma. 
     
     
         19 - 20 . (canceled) 
     
     
         21 . A method, comprising:
 determining whether a tumor in a subject has one or more drug resistant cells,   administering to the subject a therapeutically acceptable amount of an autophagy inhibitor and a glycolytic inhibitor in conjunction with an anti-cancer agent, if the subject has one or more drug resistant cells.   
     
     
         22 . The method of  claim 21 , wherein the drug sensitive tumor is a melanoma. 
     
     
         23 . The method of  claim 21 , wherein the drug sensitive tumor is an ovarian tumor. 
     
     
         24 . The method of  claim 21 , wherein the drug sensitive tumor is a glioblastoma. 
     
     
         25 - 31 . (canceled)