Combined tumor suppressor gene therapy and chemotherapy in the treatment of neoplasms

Abstract

In one embodiment, this invention provides methods of treating mammalian cancer or hyperproliferative cells, said method comprising contacting said cells with a tumor suppressor protein or tumor suppressor nucleic acid and also contacting said cell with at least one adjunctive anti-cancer agent. The invention also provides for a pharmacological composition comprising a tumor suppressor protein or a tumor suppressor nucleic acid and at least one adjunctive anti-cancer agent, and a kit for the treatment of mammalian cancer or hyperproliferative cells.

1 . A method of treating mammalian cancer cells deficient in functional p53, comprising contacting the cancer cells with a p53 tumor suppressor protein, and also contacting the cells with the polyprenyl-protein transferase inhibitor FPT39, such that one or more disease characteristics of the cells are ameliorated, wherein the mammalian cancer cells are human breast, colorectal, pancreatic, or prostate cancer cells.  
     
     
         2 . The method of  claim 1 , wherein the cells are first contacted with the p53 tumor suppressor protein and are subsequently contacted with the FPT39.  
     
     
         3 . The method of  claim 1 , wherein the cells are first contacted with the FPT39 and subsequently contacted with the p53 tumor suppressor protein.  
     
     
         4 . The method of  claim 1 , wherein the cells are simultaneously contacted with the FPT39 and with the p53 tumor suppressor protein.  
     
     
         5 . The method of  claim 1 , wherein the p53 tumor suppressor protein is dispersed in a pharmacologically acceptable excipient.  
     
     
         6 . The method of  claim 1 , wherein the p53 tumor suppressor protein and the FPT39 are dispersed in a single composition.  
     
     
         7 . The method of  claim 1 , wherein the step of contacting the cells with the p53 tumor suppressor protein comprises contacting the cells with the p53 tumor suppressor protein in a multiplicity of treatments each separated by at least about 6 hours.  
     
     
         8 . A method of treating human breast, colorectal, pancreatic, or prostate cancer cells in a mammal, the method comprising administering to the mammal a p53 tumor suppressor protein, and also administering to the mammal the polyprenyl-protein transferase inhibitor FPT39, such that one or more disease characteristics of the cancer cells are ameliorated.  
     
     
         9 . The method of  claim 8 , wherein the cancer cells comprise human breast cancer cells.  
     
     
         10 . The method of  claim 8 , wherein the cancer cells comprise human colorectal cancer cells.  
     
     
         11 . The method of  claim 8 , wherein the cancer cells comprise human pancreatic cancer cells.  
     
     
         12 . The method of  claim 8 , wherein the cancer cells comprise human prostate cancer cells.  
     
     
         13 . The method of  claim 8 , wherein the cells are first contacted with the p53 tumor suppressor protein and are subsequently contacted with the FPT39.  
     
     
         14 . The method of  claim 8 , wherein the cells are first contacted with the FPT39 and subsequently contacted with the p53 tumor suppressor protein.  
     
     
         15 . A method of treating human breast, colorectal, pancreatic, or prostate cancer cells in vitro, the method comprising contacting the cancer cells with a p53 tumor suppressor protein, and also contacting the cells with the polyprenyl-protein transferase inhibitor FPT39, such that one or more disease characteristics of the cancer cells are ameliorated.  
     
     
         16 . The method according to  claim 15 , wherein the cancer cells comprise human breast cancer cells.  
     
     
         17 . The method according to  claim 15 , wherein the cancer cells comprise human colorectal cancer cells.  
     
     
         18 . The method according to  claim 15 , wherein the cancer cells comprise human pancreatic cancer cells.  
     
     
         19 . The method according to  claim 15 , wherein the cancer cells comprise human prostate cancer cells.  
     
     
         20 . The method of  claim 15 , wherein the cells are first contacted with the FPT39 and subsequently contacted with the p53 tumor suppressor protein.