Cancer treatment
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. The STAT (signal transducers and activators of transcription) family of proteins are DNA-binding proteins that play a dual role in signal transduction and activation of transcription.
1. A method of treating cancer in a subject comprising administering to the subject a weekly dose of an antisense compound complementary to a nucleic acid encoding human STAT3, wherein the antisense compound comprises a modified oligonucleotide consisting of 12 to 30 linked nucleosides having a nucleobase sequence comprising the sequence of SEQ ID NO: 12; and wherein the dose comprises about 1.5 to 3.5 milligrams of the antisense compound per kilogram of the subject's body weight per week (1.5 to 3.5 mg/kg/wk).
2. The method of claim 1 , wherein the dose is 3.0 milligrams of the antisense compound per kilogram of the subject's body weight per week (3.0 mg/kg/wk).
3. The method of claim 1 , wherein the dose is administered for at least 1 to 52 weeks.
4. The method of claim 1 , wherein the dose is administered to the subject 1 to 6 times per week.
5. The method of claim 1 , wherein the cancer is B-cell lymphoma or hepatocellular carcinoma (HCC).
6. The method of claim 5 , wherein the B-cell lymphoma is a non-Hodgkin's B-cell lymphoma.
7. The method of claim 6 , wherein the non-Hodgkin's B-cell lymphoma is diffuse large B cell lymphoma (DLBCL).
8. The method of claim 1 , wherein the modified oligonucleotide is single-stranded consisting of 16 linked nucleosides having a nucleobase sequence consisting of SEQ ID NO: 12, comprising:
a gap segment consisting of ten linked 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 a 5-methylcytosine.