Cancer treatment

Abstract

In certain embodiments, methods, compounds, and compositions for treating B-cell lymphoma or hepatocellular carcinoma by inhibiting expression of STAT3 mRNA or protein in an animal are provided herein. Such methods, compounds, and compositions are useful to treat, prevent, or ameliorate B-cell lymphoma or hepatocellular carcinoma.

1 . A method of treating cancer in a subject comprising administering to the subject a weekly dose of about 1.5 to 3.5 milligrams of a sodium salt of a single-stranded modified oligonucleotide per kilogram of the subject's body weight per week (1.5-3.5 mg/kg/wk), wherein the modified oligonucleotide consists of 16 linked nucleosides, has a nucleobase sequence consisting of the nucleobase sequence of SEQ ID NO: 12, and has:
 a gap segment consisting of ten linked 2′-deoxynucleosides;   a 5′ wing segment consisting of 3 linked nucleosides; and   a 3′ wing segment consisting of 3 linked nucleosides;   
       wherein the gap segment is positioned between the 5′ wing segment and the 3′ wing segment wherein each nucleoside of each wing segment comprises a constrained ethyl nucleoside; wherein each internucleoside linkage of the modified oligonucleotide is a phosphorothioate linkage; and wherein each cytosine of the modified oligonucleotide is 5-methylcytosine. 
     
     
         2 . A method of treating cancer in a subject comprising administering to the subject about 15 milligrams to 250 milligrams per week of a sodium salt of a single-stranded modified oligonucleotide consisting of 16 linked nucleosides and having a nucleobase sequence consisting of the nucleobase sequence of SEQ ID NO: 12, wherein the modified oligonucleotide has:
 a gap segment consisting of ten linked 2′-deoxynucleosides;   a 5′ wing segment consisting of 3 linked nucleosides; and   a 3′ wing segment consisting of 3 linked nucleosides;   
       wherein the gap segment is positioned between the 5′ wing segment and the 3′ wing segment; wherein each nucleoside of each wing segment comprises a constrained ethyl nucleoside; wherein each internucleoside linkage of the modified oligonucleotide is a phosphorothioate linkage; and wherein each cytosine of the modified oligonucleotide is 5-methylcytosine. 
     
     
         3 . (canceled) 
     
     
         4 . The method of  claim 1 , wherein 3.0 milligrams of the sodium salt of the single-stranded modified oligonucleotide is administered to the subject per kilogram of the subject's body weight per week (3.0 mg/kg/wk). 
     
     
         5 - 10 . (canceled) 
     
     
         11 . The method of  claim 1 , wherein the cancer is B-cell lymphoma or hepatocellular carcinoma (HCC). 
     
     
         12 . The method of  claim 11 , wherein the B-cell lymphoma is a non-Hodgkin's B-cell lymphoma. 
     
     
         13 . The method of  claim 12 , wherein the non-Hodgkin's B-cell lymphoma is selected from the group consisting of: diffuse large B cell lymphoma (DLBCL), follicular lymphoma, mucosa-associated lymphatic tissue lymphoma (MALT), small cell lymphocytic lymphoma, chronic lymphocytic leukemia, mantle cell lymphoma (MCL), Burkitt lymphoma, mediastinal large B cell lymphoma, Waldenstrom macroglobulinemia, nodal marginal zone B cell lymphoma (NMZL), splenic marginal zone lymphoma (SMZL), intravascular large B-cell lymphoma, primary effusion lymphoma, and lymphomatoid granulomatosis. 
     
     
         14 . The method of  claim 12 , wherein the non-Hodgkin's B-cell lymphoma is diffuse large B cell lymphoma (DLBCL). 
     
     
         15 - 31 . (canceled) 
     
     
         32 . The method of  claim 2 , wherein the cancer is B-cell lymphoma or hepatocellular carcinoma (HCC). 
     
     
         33 . The method of  claim 32 , wherein the B-cell lymphoma is a non-Hodgkin's B-cell lymphoma. 
     
     
         34 . The method of  claim 33 , wherein the non-Hodgkin's B-cell lymphoma is selected from the group consisting of: diffuse large B cell lymphoma (DLBCL), follicular lymphoma, mucosa-associated lymphatic tissue lymphoma (MALT), small cell lymphocytic lymphoma, chronic lymphocytic leukemia, mantle cell lymphoma (MCL), Burkitt lymphoma, mediastinal large B cell lymphoma, Waldenstrom macroglobulinemia, nodal marginal zone B cell lymphoma (NMZL), splenic marginal zone lymphoma (SMZL), intravascular large B-cell lymphoma, primary effusion lymphoma, and lymphomatoid granulomatosis. 
     
     
         35 . The method of  claim 33 , wherein the non-Hodgkin's B-cell lymphoma is diffuse large B cell lymphoma (DLBCL).