Compositions and methods for treatment of ovarian cancer

Abstract

The disclosure provides compositions and methods for treating an ovarian cancer in a subject. More specifically, the disclosure provides microRNA (miRNA) inhibitor molecules that target to different miRNAs for treating different types of ovarian cancers in a subject. Furthermore, different modifications of miRNA inhibitor molecules as well as different derivatives of miRNA inhibitor molecules are also described.

1 . A method of inhibiting proliferation of ovarian cancer cells, the method comprising introducing into the cells a compound which inhibit expression or activity of a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-40 and sequences at least about 80% identical thereto. 
     
     
         2 . The method of  claim 1 , wherein the compound comprising a modified oligonucleotide consisting of 15 to 30 linked nucleosides, wherein the modified oligonucleotide has a nucleobase sequence that is complementary to a nucleobase sequence selected from SEQ ID NOs: 1-40; or to a sequence at least 80% identical thereto. 
     
     
         3 . The method of  claim 2 , wherein said modified oligonucleotide has a nucleobase sequence selected from SEQ ID NOs: 41-58; or to a sequence at least 80% identical thereto. 
     
     
         4 . The method of  claim 1 , wherein the ovarian cancer cell is selected from the group consisting of serous and endometrioid ovarian cancer. 
     
     
         5 . A method for treating ovarian cancer, comprising administering to a subject in need thereof a pharmaceutical composition comprising a modified oligonucleotide consisting of 15 to 30 linked nucleosides, wherein the modified oligonucleotide has a nucleobase sequence that is complementary to a nucleobase sequence selected from SEQ ID NOs: 1-40; or to a sequence at least 80% identical thereto. 
     
     
         6 . The method of  claim 5 , wherein the modified oligonucleotide has a nucleobase sequence comprising at least 15 contiguous nucleobases of a nucleobase sequence selected from among the nucleobase sequences recited in SEQ ID NOs: 41-58; or a sequence at least 80% identical thereto. 
     
     
         7 . The method of  claim 5 , wherein the subject is a human. 
     
     
         8 . The method of  claim 5 , wherein the ovarian cancer is selected from the group consisting of serous and endometrioid ovarian cancer. 
     
     
         9 . The method of any of  claims 1 - 8 , wherein the nucleobase sequence of the modified oligonucleotide has no more than two mismatches to a nucleobase sequence selected from SEQ ID NOs: 41-58. 
     
     
         10 . The method of any of  claims 1 - 8 , wherein the nucleobase sequence of the modified oligonucleotide has no more than one mismatch to a nucleobase sequence selected from SEQ ID NO: 41-58. 
     
     
         11 . The method of any of  claims 1 - 8 , wherein the nucleobase sequence of the modified oligonucleotide has one mismatch to a nucleobase sequence selected from SEQ ID NO: 41-58. 
     
     
         12 . The method of any of  claims 1 - 8 , wherein the nucleobase sequence of the modified oligonucleotide has no mismatch to a nucleobase sequence selected from SEQ ID NO: 41-58. 
     
     
         13 . The method of any of  claims 1 - 12 , wherein at least one internucleoside linkage is a modified internucleoside linkage. 
     
     
         14 . The method of any of  claims 1 - 13 , wherein each internucleoside linkage is a modified internucleoside linkage. 
     
     
         15 . The method of any of  claims 1 - 15 , wherein at least one internucleoside linkage is a phosphorothioate internucleoside linkage. 
     
     
         16 . The method of any of  claims 1 - 16 , wherein each internucleoside linkage is a phosphorothioate internucleoside linkage. 
     
     
         17 . The method of any of  claims 1 - 17 , wherein at least one nucleoside comprises a modified sugar. 
     
     
         18 . The method of any of  claims 1 - 13 , wherein each of a plurality of nucleosides comprises a modified sugar. 
     
     
         19 . The method of any of  claims 1 - 14 , wherein each nucleoside comprises a modified sugar. 
     
     
         20 . The method of any of  claims 1 - 15 , wherein each nucleoside comprises a 2′-O-methoxyethyl sugar. 
     
     
         21 . The method of any of  claims 5 - 20 , wherein the administering comprises intravenous administration, subcutaneous administration, intratumoral administration, or chemoembolization. 
     
     
         22 . The method of any of  claims 5 - 21 , further comprising administering at least one additional therapy. 
     
     
         23 . The method of  claim 22 , wherein the at least one additional therapy is a chemotherapeutic agent. 
     
     
         24 . The method of  claim 23 , wherein the chemotherapeutic agent may be selected from cisplatin, carboplatin, camptothecins, doxorubicin, cyclophosphamide, paclitaxel, etoposide, vinblastine, Actinomycin D and cloposide. 
     
     
         25 . The method of  claim 22 , wherein the at least one additional therapy is administered at the same time as the modified oligonucleotide. 
     
     
         26 . The method of  claim 22 , wherein the at least one additional therapy is administered less frequently than the modified oligonucleotide. 
     
     
         27 . The method of  claim 22 , wherein the at least one additional therapy is administered more frequently than the modified oligonucleotide. 
     
     
         28 . The method of any of  claims 5 - 27 , wherein the modified oligonucleotide is administered at a dose selected from 50, 75, 100, 125, 150, 175, 200, 225, 250, 275, 300, 325, 350, 375, 400, 425, 450, 475, 500, 525, 550, 575, 600, 625, 650, 675, 700, 725, 750, 775, and 800 mg. 
     
     
         29 . The method of any of  claims 5 - 28 , wherein the modified oligonucleotide is administered one per day, once per week, once per two weeks, once per three weeks, or once per four weeks. 
     
     
         30 . The method of any of  claims 5 - 29 , wherein the administering results in reduction of tumor size. 
     
     
         31 . The method of any of  claims 5 - 30 , wherein the administering results in reduction of tumor number. 
     
     
         32 . The method of any of  claims 5 - 31 , wherein the administering prevents an increase in tumor size. 
     
     
         33 . The method of any of  claims 5 - 32 , wherein the administering prevents an increase in tumor number. 
     
     
         34 . The method of any of  claims 5 - 33 , wherein the administering prevents metastatic progression. 
     
     
         35 . The method of any of  claims 5 - 34 , wherein the administering slows or stops metastatic progression.