SNS-595 and methods of using the same

Abstract

The present invention relates to SNS-595 and methods of treating cancer using the same.

1 . A method for determining whether a cancer to be treated will respond SNS-595 treatment comprising determining a first amount of at least one member of the DNA-PK pathway in cells of the cancer to be treated and comparing the first amount to a second amount.  
   
   
       2 . The method of  claim 1  wherein the first amount is the pretreatment amount and the second amount is the amount of the member of the DNA-PK pathway in normal cells derived from the same tissue as the cancer to be treated.  
   
   
       3 . The method of  claim 2  wherein the member of the DNA-PK pathway is selected from DNA-PK, Ku70, Ku80, MRE11, NBS 1, RAD50, XRCC4, ligase IV, H2AX, c-Abl, p73, caspase-9 and caspase-3.  
   
   
       4 . The method of  claim 1  wherein the first amount is the pretreatment amount and the second amount is the post-treatment amount.  
   
   
       5 . The method of  claim 4  wherein the member of the DNA-PK pathway is selected from DNA-PK, Ku70, Ku80, MRE11, NBS1, RAD50, XRCC4, ligase IV, H2AX, c-Abl, p73, caspase-9 and caspase-3.  
   
   
       6 . The method of  claim 4  wherein the member of the DNA-PK pathway is DNA-PK.  
   
   
       7 . The method of  claim 4  wherein the member of the DNA-PK pathway is Ku70.  
   
   
       8 . The method of  claim 4  wherein the member of the DNA-PK pathway is Ku80.  
   
   
       9 . The method of  claim 4  wherein the member of the DNA-PK pathway is p73.  
   
   
       10 . A combination for cancer treatment comprising: 
 a) a therapeutically effective amount of SNS-595 and    b) a therapeutically effective amount of a second agent whose cytotoxicity is also mediated through the DNA-PK pathway.    
   
   
       11 . The combination of  claim 10  wherein the second agent is an agent that inhibits nonhomologous endjoining repair.  
   
   
       12 . The combination of  claim 11  wherein the second agent is a DNA-PK inhibitor.  
   
   
       13 . The combination of  claim 11  wherein the second agent is a ligase IV inhibitor.  
   
   
       14 . The combination of  claim 10  wherein the second agent is an apoptosis enhancing agent.  
   
   
       15 . The combination of  claim 14  wherein the second agent is a caspase-9 activator.  
   
   
       16 . The combination of  claim 14  wherein the second agent is a caspase-3 activator.  
   
   
       17 . The combination of  claim 14  wherein the second agent is a Hsp90 inhibitor.  
   
   
       18 . A combination comprising: 
 a) a therapeutically effective amount of SNS-595 and    b) a therapeutically effective amount of a second agent that is capable of impeding DNA synthesis.    
   
   
       19 . The combination of  claim 18  wherein the second agent is an alkylating agent.  
   
   
       20 . The combination of  claim 19  wherein the alkylating agent is a nitrogen mustard, alkyl sulfonate, nitrosourea, or a triazene.  
   
   
       21 . The combination of  claim 18  wherein the second agent is an anti-neoplastic antibiotic.  
   
   
       22 . The combination of  claim 18  wherein the second agent is an anti-metabolite.  
   
   
       23 . The combination of  claim 22  wherein the antimetabolite is a folate analog, purine analog, adenosine analog, pyrimidine analog or hydroxyurea.  
   
   
       24 . The combination of  claim 18  wherein the second agent is a platinum coordination complex.  
   
   
       25 . The combination of  claim 18  wherein the second agent is a topoisomerase II inhibitor.  
   
   
       26 . The combination of  claim 18  wherein the second agent is radiation.