Treatment of Cancers with Micro-RNA Inhibitors

Abstract

The invention relates to the treatment and prevention of cancers, including blood-based cancers and breast cancers, by administering agents that inhibit the activity of microRNAs, including miR-22. Inhibitors can include oligonucleotides that are at least partially complementary to these miRNAs. In some embodiments, these inhibitors are chemically modified oligonucleotides, including locked nucleic acids (LNAs).

1 . A method of treating or preventing cancer in a subject in need thereof, comprising administering to the subject an inhibitor of miR-22, wherein the cancer is selected from a blood-based cancer or breast cancer. 
     
     
         2 . The method of  claim 1 , wherein the inhibitor is an antisense oligonucleotide. 
     
     
         3 . The method of  claim 1 , wherein expression and/or activity of miR-22 is reduced in the subject following administration of the inhibitor. 
     
     
         4 . The method of  claim 1 , wherein the inhibitor comprises is an antisense oligonucleotide comprising a sequence that is at least partially complementary to a mature sequence of miR-22. 
     
     
         5 . The method of  claim 1 , wherein one or more nucleotides of the inhibitor are chemically modified, wherein the chemical modification is selected from locked nucleic acid (LNA), phosphorothioate, 2′-O-Methyl, 2′-O-Methoxyethyl, 2′-O-alkyl-RNA unit, 2′-OMe-RNA unit, 2′-amino-DNA unit, 2′-fluoro-DNA unit, peptide nucleic acid (PNA) unit, hexitol nucleic acids (HNA) unit, INA unit, and a 2′-O-(2-Methoxyethyl)-RNA (2′ MOE RNA) unit. 
     
     
         6 . (canceled) 
     
     
         7 . The method of  claim 2 , wherein the antisense oligonucleotide comprises 16 or fewer nucleotides. 
     
     
         8 . The method of  claim 7 , wherein the antisense oligonucleotide is about 7 to about 8 nucleotides. 
     
     
         9 . The method of  claim 1 , wherein the inhibitor of miR-22 prevents the deregulation of ten-eleven-translocation gene 2 (TET2). 
     
     
         10 . (canceled) 
     
     
         11 . The method of  claim 1 , wherein the blood-based cancer is a leukemia, lymphoma, myeloma or myelodysplastic/myeloproliferative neoplasm (MDS/MPN). 
     
     
         12 . The method of  claim 11 , wherein the leukemia is acute lymphocytic leukemia (ALL), acute myelogenous leukemia (AML), chronic lymphocytic leukemia (CLL), or chronic myelogenous leukemia (CML). 
     
     
         13 . The method of  claim 11 , wherein the lymphoma is a Hodgkin lymphoma or a non-Hodgkin lymphoma. 
     
     
         14 . The method of  claim 11 , wherein the myeloma is IgG, IgE, IgA, IgM, IgD, light chain, or non-secretory myeloma. 
     
     
         15 . The method of  claim 1 , wherein the breast cancer is one or more of ER + , PR + , HER2 + , AR + , and PRLr +  or is one or more of ER−, PR−, HER2−, AR−, and PRLr−. 
     
     
         16 . (canceled) 
     
     
         17 . The method of  claim 1 , wherein the subject is a mammal or a human. 
     
     
         18 . (canceled) 
     
     
         19 . A method of preventing metastasis in a subject in need thereof, comprising administering an effective amount of an inhibitor of miR-22. 
     
     
         20 . (canceled) 
     
     
         21 . The method of  claim 19 , wherein the inhibitor of miR-22 is an antisense oligonucleotide. 
     
     
         22 . The method of  claim 19 , wherein expression and/or activity of miR-22 is reduced in the subject following administration of the inhibitor. 
     
     
         23 . The method of  claim 19 , wherein the inhibitor comprises is an antisense oligonucleotide comprising a sequence that is at least partially complementary to a mature sequence of miR-22. 
     
     
         24 . The method of  claim 19 , wherein one or more nucleotides of the inhibitor are chemically modified, wherein the chemical modification is optionally, selected from locked nucleic acid (LNA), phosphorothioate, 2′-O-Methyl, 2′-O-Methoxyethyl, 2′-O-alkyl-RNA unit, 2′-OMe-RNA unit, 2′-amino-DNA unit, 2′-fluoro-DNA unit, peptide nucleic acid (PNA) unit, hexitol nucleic acids (HNA) unit, INA unit, and a 2′-O-(2-Methoxyethyl)-RNA (2′ MOE RNA) unit. 
     
     
         25 - 26 . (canceled) 
     
     
         27 . The method of  claim 21 , wherein the antisense oligonucleotide is about 7 to about 8 nucleotides.