Compounds for the modulation of beta-catenin expression

Abstract

The invention relates to oligomer compounds (oligomers), which target beta-catening mRNA in a cell, leading to reduced expression of beta-catenin. Reduction of beta-catenin expression is beneficial for a range of medical disorders, such as hyperproliferative disorders, such as cancer. The invention provides therapeutic compositions comprising oligomers and methods for modulating the expression of beta-catenin using said oligomers, including methods of treatment.

1 . A method of treating cancer in a mammal, comprising administering to said mammal an effective amount of an oligomer
 wherein said oligomer has the formula:   
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 168) 
                 
                     
                   5′- Me C s   Me C s A s t s c s t s t s g s t s g s a s t s c s   Me C s A s T-3′; 
                 
                     
                   and 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 171) 
                 
                     
                   5′-G s T s G s t s t s c s t s a s c s a s c s c s a s T s T s A-3′, 
                 
             
                
                
                
                
                
                
               
            
           
         
         
           wherein uppercase letters denote beta-D-oxy-LNA monomers, lowercase letters denote DNA monomers, the subscript “s” denotes a phosphorothioate linkage, and  Me C denotes a beta-D-oxy-LNA monomer containing a 5-methylcytosine base. 
         
       
     
     
         2 . The method of  claim 1 , wherein the cancer is selected from the group consisting of colorectal cancer, hepatocellular cancer, endometrial cancer, malignant melanoma, ovarian cancer, pancreatic cancer, pituitary cancer, esophageoal cancer, lung cancer, breast cancer, kidney cancer, hematopoietic system cancer, cervical cancer, central nervous system cancer, bone cancer, biliary tract cancer and adrenal gland cancer. 
     
     
         3 . The method of  claim 2 , wherein the cancer is colorectal cancer. 
     
     
         4 . The method of  claim 2 , where the cancer is breast cancer.