Cancer therapy comprising deaminase enzyme inhibitors

Abstract

The present invention provides materials and methods for the treatment of neoplastic disease states, especially cancers of cells/organs of epithelial origin. For example, the invention provides chemotherapeutic materials and methods for treatment comprising an inhibitor of at least one of the enzymes adenosine deaminase and AMP deaminase.

What is claimed is:  
     
         1 . A method of inducing cell death in tumor cells, comprising administering to a human subject a composition comprising a compound selected from the group consisting of adenosine deaminase inhibitors (ADAI), adenosine monophosphate deaminase inhibitors (AMPDAI), and pharmaceutically acceptable salts thereof, wherein the human subject has a tumor with elevated adenosine in the tumor cells or in extracellular fluid of the tumor, and wherein the composition is administered in an amount sufficient to induce cell death in cells of the tumor.  
     
     
         2 . A method of inducing cell death in tumor cells, comprising: 
 screening a human subject for elevated adenosine in a tumor or in extracellular fluid of a tumor, and    administering to a human subject diagnosed with the tumor with the elevated adenosine a composition comprising a compound selected from the group consisting of adenosine deaminase inhibitors (ADAI), adenosine monophosphate deaminase inhibitors (AMPDAI), and pharmaceutically acceptable salts thereof, wherein the composition is administered in an amount sufficient to induce cell death in cells of the tumor.    
     
     
         3 . A method according to  claim 1  or  2  wherein the composition further comprises a pharmaceutically acceptable carrier.  
     
     
         4 . A method according to  claim 1  or  2 , further comprising administering to the subject homocysteine in an amount effective to potentiate the inducing cell death by said composition.  
     
     
         5 . A method according to  claim 1  or  2  wherein the compound has both ADAI and AMPDAI activity.  
     
     
         6 . A method according to  claim 1  or  2  wherein the compound is deoxycoformycin (dCF).  
     
     
         7 . A method according to  claim 1  or  2  wherein the compound is coformycin (CF).  
     
     
         8 . A method according to  claim 1  or  2  wherein the neoplastic disease state is an epithelial malignancy.  
     
     
         9 . A method according to  claim 1  or  2  wherein the tumor is selected from malignancies of the lungs, breasts, gastrointestinal system, genitourinary tract, or reproductive organs.  
     
     
         10 . A method according to  claim 1  or  2  wherein the tumor is ovarian.  
     
     
         11 . A method according to  claim 1  or  2  wherein the composition is administered in a unit dose to effect a higher concentration of the composition in or around said tumor than in the peripheral blood.  
     
     
         12 . A method according to  claim 11  wherein the tumor is situated in the peritoneal cavity, and wherein the administering step comprises infusing or injecting the composition into the peritoneal cavity.  
     
     
         13 . A method according to  claim 12  wherein the infusing is performed through a catheter inserted into the peritoneal cavity.  
     
     
         14 . A method according to  claim 13  wherein the unit dose is administered at concentrations effective to maintain a peritoneal concentration of the compound of at least 5 μM for at least 12 hours.  
     
     
         15 . A method according to  claim 13  wherein the unit dose is administered at concentrations effective to maintain a peritoneal concentration of the compounds of about 5 μM -20 μM for at least 12 hours.  
     
     
         16 . A method according to  claim 13  wherein the unit dose is administered at concentrations effective to inhibit adenosine deaminases for at least about 12 to about 96 hours.  
     
     
         17 . A method according to  claim 11 , further comprising the step of systemically administering to said patient a composition comprising a protective agent selected from the group consisting of a nucleoside transport inhibitor, an adenosine kinase inhibitor, combination thereof, and pharmaceutically acceptable salts thereof, in an amount effective to reduce systemic side effects of said compound.  
     
     
         18 . A method according to  claim 2  wherein the composition is administered in a unit dose to effect a higher concentration of the composition in or around said tumor than in the peripheral blood.  
     
     
         19 . A method according to  claim 18  wherein the tumor is situated in the peritoneal cavity, and wherein the administering step comprises infusing or injecting the composition into the peritoneal cavity.  
     
     
         20 . A method according to  claim 19  wherein the infusing is performed through a catheter inserted into the peritoneal cavity.  
     
     
         21 . A method according to  claim 20  wherein the unit dose is administered at concentrations effective to maintain a peritoneal concentration of the compound of at least 5 μM for at least 12 hours.  
     
     
         22 . A method according to  claim 20  wherein the unit dose is administered at concentrations effective to maintain a peritoneal concentration of the compounds of about 5 μM -20 μM for at least 12 hours.  
     
     
         23 . A method according to  claim 20  wherein the unit dose is administered at concentrations effective to inhibit adenosine deaminases for at least about 12 to about 96 hours.  
     
     
         24 . A method according to  claim 18 , further comprising the step of systemically administering to said patient a composition comprising a protective agent selected from the group consisting of a nucleoside transport inhibitor, an adenosine kinase inhibitor, combination thereof, and pharmaceutically acceptable salts thereof, in an amount effective to reduce systemic side effects of said compound.  
     
     
         25 . A kit for treating a neoplastic disease state comprising a container holding a compound selected from the group consisting of adenosine deaminase inhibitors (ADAI), adenosine monophosphate deaminase inhibitors (AMPDAI), combinations thereof, and pharmaceutically acceptable salts thereof and a label attached to or packaged with the container, the label describing use of the compound for inducing cell death in tumors with elevated adenosine.