Treatment of cancers with micro-RNA inhibitors
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 cancer, comprising administering to a subject in need thereof an inhibitor of miR-22, wherein the inhibitor is an antisense oligonucleotide of at least 7 nucleotides in length that is 100% complementary over its entire length to a miR-22 sequence, and wherein the cancer is selected from a blood-based cancer or breast cancer that overexpresses miR-22 relative to normal blood or breast cells or tissues.
2. The method of claim 1 , wherein one or more nucleotides of the inhibitor are chemically modified and 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.
3. The method of claim 1 , wherein the antisense oligonucleotide comprises 16 or fewer nucleotides.
4. The method of claim 1 , wherein the blood-based cancer is a leukemia, lymphoma, myeloma or myelodysplastic/myeloproliferative neoplasm (MDS/MPN).
5. The method of claim 4 , wherein the leukemia is acute lymphocytic leukemia (ALL), acute myelogenous leukemia (AML), chronic lymphocytic leukemia (CLL), or chronic myelogenous leukemia (CML).
6. The method of claim 4 , wherein the lymphoma is a Hodgkin lymphoma or a non-Hodgkin lymphoma.
7. The method of claim 4 , wherein the myeloma is IgG, IgE, IgA, IgM, IgD, light chain, or non-secretory myeloma.
8. The method claim 1 , wherein the breast cancer is one or more of ER + , PR + , HER2 + , AR + , and PRLr + .
9. The method of claim 1 , wherein the breast cancer is one or more of ER − , PR − , HER2 − , AR − , and PRLr − .
10. A method of preventing metastasis, comprising administering an effective amount of an inhibitor of miR-22 to a subject having cancer, wherein the inhibitor is an antisense oligonucleotide of at least 7 nucleotides in length comprising a sequence that is 100% complementary over its length to a miR-22 sequence, and wherein the cancer is selected from a blood-based cancer or breast cancer that overexpresses miR-22 relative to normal blood or breast cells or tissues.