Compositions and methods for the treatment of a beta-catenin-associated disease or disorder

Abstract

Disclosed herein are methods for the treatment of cancer, comprising administering to a subject a β-catenin nucleic acid inhibitor molecule and a therapeutically effective amount of an MEK inhibitor or a c-Myc nucleic acid inhibitor molecule. Also disclosed herein is a pharmaceutical composition comprising a therapeutically effective amount of a β-catenin nucleic acid inhibitor molecule; a therapeutically effective amount of an MEK inhibitor or a c-Myc nucleic acid inhibitor molecule and at least one pharmaceutical carrier.

1 .- 44 . (canceled) 
     
     
         45 . A method of treating a β-catenin-associated cancer in a subject, comprising administering to the subject: a therapeutically effective amount of a β-catenin nucleic acid inhibitor molecule; and a therapeutically effective amount of a c-Myc nucleic acid inhibitor molecule. 
     
     
         46 . The method of  claim 45 , wherein the β-catenin-associated cancer is colorectal cancer, hepatocellular carcinoma, or melanoma. 
     
     
         47 . The method of  claim 45 , wherein the subject is a human. 
     
     
         48 . The method of  claim 45 , wherein the β-catenin nucleic acid inhibitor molecule is a dsRNAi inhibitor molecule. 
     
     
         49 . The method of  claim 45 , wherein the β-catenin nucleic acid inhibitor molecule is a dsRNAi inhibitor molecule, wherein the double-stranded region of the molecule is between 15 and 40 nucleotides in length. 
     
     
         50 . The method of  claim 45 , wherein the β-catenin nucleic acid inhibitor molecule is a dsRNAi inhibitor molecule comprising a sense and an antisense strand and a duplex region of between 18 and 40 nucleotides, wherein the sense strand is 25-34 nucleotides in length and the antisense strand is 26-38 nucleotides in length and comprises 1-5 single-stranded nucleotides at its 3′ terminus. 
     
     
         51 . The method of  claim 50 , wherein the sense strand comprises the sequence of SEQ ID NO: 1. 
     
     
         52 . The method of  claim 50 , wherein the antisense strand comprises the sequence of SEQ ID NO: 2. 
     
     
         53 . The method of  claim 45 , wherein the c-Myc nucleic acid inhibitor molecule is a dsRNAi inhibitor molecule. 
     
     
         54 . The method of  claim 45 , wherein the c-Myc nucleic acid inhibitor molecule is a dsRNAi inhibitor molecule, wherein the double-stranded region of the molecule is between 15 and 40 nucleotides in length. 
     
     
         55 . The method or composition of  claim 54 , wherein the c-Myc nucleic acid inhibitor molecule is a dsRNAi inhibitor molecule comprising a sense and antisense strand and a duplex region of between 18 and 40 nucleotides, wherein the sense strand is 25-34 nucleotides in length and the antisense strand is 26-38 nucleotides in length and comprises 1-5 single-stranded nucleotides at its 3′ terminus. 
     
     
         56 . The method or composition of  claim 55 , wherein the sense strand of the c-Myc dsRNAi inhibitor molecule comprises the sequence of SEQ ID NO: 3. 
     
     
         57 . The method of  claim 55 , wherein the antisense strand of the c-Myc dsRNAi inhibitor molecule comprises the sequence of SEQ ID NO: 4. 
     
     
         58 . The method of  claim 55 , wherein the sense strand of the c-Myc dsRNAi inhibitor molecule comprises the sequence of SEQ ID NO: 5. 
     
     
         59 . The method of  claim 55 , wherein the antisense strand of the c-Myc dsRNAi inhibitor molecule comprises the sequence of SEQ ID NO: 6. 
     
     
         60 . The method of  claim 45 , wherein the β-catenin nucleic acid inhibitor molecule and/or the c-Myc nucleic acid inhibitor molecule is formulated with a lipid nanoparticle. 
     
     
         61 . The method of  claim 60 , wherein the lipid nanoparticle comprises a cationic lipid and a pegylated lipid. 
     
     
         62 . A method of treating a β-catenin-associated cancer in a subject, comprising administering to the subject: a therapeutically effective amount of a β-catenin nucleic acid inhibitor molecule; and a therapeutically effective amount of a c-Myc nucleic acid inhibitor molecule, wherein the β-catenin nucleic acid inhibitor molecule is a dsRNAi inhibitor molecule and wherein the c-Myc nucleic acid inhibitor molecule is a dsRNAi inhibitor molecule. 
     
     
         63 . A method of treating a β-catenin-associated cancer in a subject, comprising administering to the subject: a therapeutically effective amount of a β-catenin nucleic acid inhibitor molecule; and a therapeutically effective amount of a c-Myc nucleic acid inhibitor molecule, wherein the β-catenin nucleic acid inhibitor molecule is a dsRNAi inhibitor molecule with a sense strand comprising SEQ ID NO: 1 and an antisense strand comprising SEQ ID NO: 2, and wherein the c-Myc nucleic acid inhibitor molecule is a dsRNAi inhibitor molecule with a sense strand comprising SEQ ID NO: 3 or 5 and an antisense strand comprising SEQ ID NO: 4 or 6. 
     
     
         64 . The method of  claim 63 , wherein prior to administering the β-catenin nucleic acid inhibitor molecule, the subject has undergone at least three, four, five, or six administrations of a prior treatment for the β-catenin-associated cancer. 
     
     
         65 . The method of  claim 64 , wherein the β-catenin-associated cancer has metastasized. 
     
     
         66 . The method of  claim 65 , wherein the β-catenin-associated cancer is colorectal cancer. 
     
     
         67 . The method of  claim 65 , wherein the colorectal cancer has metastasized to the liver.