Compositions and methods for treating cancers

Abstract

The present invention relates to compositions and methods for treating of cancer. In some embodiments, the invention relates to the use of agents that can modulate a component in the CDX2-KLF4 signaling pathway to treat myelodysplastic syndromes (MDS), acute myelogenous leukemia (AML), acute lymphocytic leukemia (ALL), adult T-cell leukaemia (ATLL), lymphoma, gastric cancer, multiple myeloma, or combinations thereof, or a condition associated with abnormal activity of the CDX2-KLF4 signaling pathway.

1 . A method of treating myelodysplastic syndrome (MDS) in a human subject, comprising administering to a human subject in need of such treatment an effective amount of a compound or a pharmacologically acceptable salt or solvate thereof, said compound having formula I: 
       
         
           
           
               
               
           
         
         wherein
 R 1  is C 1 -C 4  alkyl; and 
 R 2  is halogen. 
 
       
     
     
         2 . The method of  claim 1 , wherein the human subject has an ineffective production of myeloid blood cells. 
     
     
         3 . The method of  claim 1 , wherein the human subject has an anemia. 
     
     
         4 . The method of  claim 1 , wherein the human subject has low blood counts caused by bone marrow failure. 
     
     
         5 . The method of  claim 1 , wherein R 1  is methyl, isopropyl, or t-butyl. 
     
     
         6 . The method of  claim 5 , wherein said compound has a formula selected from the group consisting of 
       
         
           
           
               
               
           
         
       
     
     
         7 . The method of  claim 5 , wherein said compound has formula II: 
       
         
           
           
               
               
           
         
       
     
     
         8 . (canceled) 
     
     
         9 . The method of  claim 1 , wherein said MDS is high-risk MDS. 
     
     
         10 . A method of treating a human subject, comprising administering to a human subject an effective amount of a compound or a pharmacologically acceptable salt or solvate thereof, wherein said human subject has a condition selected from the group consisting of acute myelogenous leukemia (AML), acute lymphocytic leukemia (ALL), adult T-cell leukaemia (ATLL), lymphoma, gastric cancer, and multiple myeloma, and wherein said compound has formula II: 
       
         
           
           
               
               
           
         
       
     
     
         11 . The method of  claim 10 , wherein said condition is AML. 
     
     
         12 . (canceled) 
     
     
         13 . (canceled) 
     
     
         14 . The method of  claim 10 , wherein said condition is ALL. 
     
     
         15 . (canceled) 
     
     
         16 . (canceled) 
     
     
         17 . (canceled) 
     
     
         18 . (canceled) 
     
     
         19 . The method of  claim 10 , wherein said condition is gastric cancer. 
     
     
         20 . The method of  claim 10 , wherein said condition is multiple myeloma. 
     
     
         21 . The method of  claim 1 , wherein said compound is administered as part of a combination therapy. 
     
     
         22 . The method of  claim 21 , wherein the combination therapy comprises radiotherapy. 
     
     
         23 . The method of  claim 21 , wherein the combination therapy comprises chemotherapy. 
     
     
         24 . The method of  claim 11 , wherein said compound is administered with a dosage of about 125 mg/m 2 . 
     
     
         25 . The method of  claim 11 , wherein said compound is administered two times per week for four weeks. 
     
     
         26 . A method of treating a condition associated with lower than normal level of KLF4 activity comprising administering to a human subject in need of such treatment an effective amount of compound has formula II: 
       
         
           
           
               
               
           
         
       
     
     
         27 . A method of treating a condition associated with abnormal level of CDX2 activity comprising administering to a human subject in need of such treatment an effective amount of compound has formula II: