Use of hydrogen sulfide synthesis inhibitors for cancer therapy

Abstract

In certain aspects the methods comprise administering an inhibitor of hydrogen sulfide biosynthesis, a cystathionine-β-synthase (CBS) inhibitor, or a hydrogen sulfide neutralizing agent to a patient having a cancer associated with elevated production of hydrogen sulfide.

1 . A method for treating cancer comprising administering a cystathionine-β-synthase (CBS) inhibitor or prodrug thereof to a patient having a cancer associated with elevated production of hydrogen sulfide. 
     
     
         2 . The method of  claim 1 , wherein the cancer is colorectal cancer. 
     
     
         3 . The method of  claim 1 , wherein the CBS inhibitor is a CBS shRNA or amino-oxyacetic acid (AOAA). 
     
     
         4 . The method of  claim 1 , wherein the prodrug is an AOAA alkyl ester. 
     
     
         5 . The method of  claim 1 , wherein the prodrug is an AOAA benzyl ester, AOAA methyl ester, or AOAA carbamate. 
     
     
         6 . The method of  claim 1 , wherein the inhibitor is administered by intra-tumoral injection. 
     
     
         7 . The method of  claim 1 , wherein the cancer has a Kras mutation. 
     
     
         8 . The method of  claim 1 , further comprising measuring H 2 S levels in a cancer sample from the patient before administering a CBS inhibitor. 
     
     
         9 . The method of  claim 1 , further comprising administering a second anti-cancer agent. 
     
     
         10 . A method of reducing hydrogen sulfide production by a cancer cell comprising administering a hydrogen sulfide neutralizing agent to the cancer cell. 
     
     
         11 . A method for treating cancer comprising administering a compound having a chemical structure of Formula I, 
       
         
           
           
               
               
           
         
         wherein R 1  is a ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, tert-butyl, n-pentyl, tert-pentyl, neo-pentyl, iso-pentyl, sec-pentyl, or 3-pentyl group; and 
         wherein the formula is administered to a patient having a cancer associated with elevated production of hydrogen sulfide. 
       
     
     
         12 . The method of  claim 11 , wherein the cancer is colorectal cancer. 
     
     
         13 . The method of  claim 11 , wherein the compound is administered by intra-tumoral injection. 
     
     
         14 . The method of  claim 11 , wherein the cancer has a Kras mutation. 
     
     
         15 . The method of  claim 11 , further comprising measuring H 2 S levels in a cancer sample from the patient before administering the compound. 
     
     
         16 . The method of  claim 11 , further comprising administering a second anti-cancer agent. 
     
     
         17 . The method of  claim 11 , wherein the compound is pentan-3-yl 2-(aminooxy)acetate (YD-2-51).