Modulation of Insulin Like Growth Factor I Receptor Expression in Cancer

Abstract

Provided herein are methods, compounds, and compositions for reducing expression of an IGF-IR mRNA and protein in an animal. Also provided herein are methods, compounds, and compositions that inhibit expression of IGF-IR in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate the tumor or cancer, or a symptom thereof.

1 . A method for the treatment of an IGF-IR positive prostate tumor or prostate cancer in a subject, the method comprising systemically administering to the subject an effective amount of an antisense oligonucleotide which inhibits expression of IGF-IR. 
     
     
         2 . The method of  claim 1 , wherein the antisense oligonucleotide comprises a sequence as provided in SEQ ID NO:43, SEQ ID NO:50, SEQ ID NO:53, SEQ ID NO:68, SEQ ID NO:73, SEQ ID NO:110, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:122, SEQ ID NO:124, SEQ ID NO:125, or SEQ ID NO:131. 
     
     
         3 . The method of  claim 1 , wherein the antisense oligonucleotide comprises a sequence as provided in SEQ ID NO:125. 
     
     
         4 . The method of  claim 1 , wherein the method further comprises treating the subject with androgen withdrawal therapy. 
     
     
         5 . The method of  claim 4 , wherein the antisense oligonucleotide is administered at about the same time that androgen withdrawal therapy is initiated. 
     
     
         6 . The method of  claim 4 , wherein the antisense oligonucleotide is administered after initiation of the androgen withdrawal therapy and before the prostate tumor or prostate cancer becomes androgen unresponsive/independent. 
     
     
         7 . The method of  claim 1 , wherein the prostate tumor or prostate cancer is resistant to a taxane based agent and/or resistant to androgen withdrawal therapy. 
     
     
         8 . The method of  claim 1 , wherein the method further comprises administering to the subject a taxane based agent. 
     
     
         9 . The method of  claim 8 , wherein the taxane based agent is Docetaxol, Larotaxel, Ortataxel, Paclitaxel, or Tesetaxel. 
     
     
         10 . A method for treating an IGF-IR positive tumor or cancer in a subject, the method comprising systemically administering to the subject an effective amount of an antisense oligonucleotide, wherein the antisense oligonucleotide comprises a sequence as provided in SEQ ID NO:125. 
     
     
         11 . The method of  claim 10 , wherein the method further comprises treating the subject with androgen withdrawal therapy. 
     
     
         12 . The method of  claim 11 , wherein the antisense oligonucleotide is administered at about the same time that androgen withdrawal therapy is initiated. 
     
     
         13 . The method of  claim 11 , wherein the antisense oligonucleotide is administered after initiation of the androgen withdrawal therapy and before the tumor or cancer becomes androgen independent. 
     
     
         14 . The method of  claim 10 , wherein the tumor or cancer is androgen unresponsive/independent. 
     
     
         15 . The method of  claim 10 , wherein the tumor or cancer is resistant to a taxane based agent. 
     
     
         16 . The method of  claim 10 , wherein the method further comprises administering to the subject a taxane based agent. 
     
     
         17 . The method of  claim 16 , wherein the taxane based agent is Docetaxol, Larotaxel, Ortataxel, Paclitaxel, or Tesetaxel. 
     
     
         18 . A method for enhancing the sensitivity of an IGF-IR positive tumor or cancer cell to a taxane based agent, the method comprising administering to the subject an effective amount of an agent that inhibits expression of IGF-IR. 
     
     
         19 . The method of  claim 18 , wherein the tumor or cancer is a prostate tumor or prostate cancer. 
     
     
         20 . The method of  claim 18 , wherein the taxane based agent is Docetaxol, Larotaxel, Ortataxel, Paclitaxel, or Tesetaxel. 
     
     
         21 . The method of  claim 18 , wherein the agent that inhibits expression of IGF-IR is an antisense oligonucleotide that comprises a sequence as provided in SEQ ID NO:43, SEQ ID NO:50, SEQ ID NO:53, SEQ ID NO:68, SEQ ID NO:73, SEQ ID NO:110, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:122, SEQ ID NO:124, SEQ ID NO:125, or SEQ ID NO:131. 
     
     
         22 . The method of  claim 19 , wherein the agent that inhibits expression of IGF-IR is an antisense oligonucleotide that comprises a sequence as provided in SEQ ID NO:125. 
     
     
         23 . The method of  claim 7 , wherein the method further comprises administering to the subject a taxane based agent. 
     
     
         24 . The method of  claim 14 , wherein the method further comprises administering to the subject a taxane based agent. 
     
     
         25 . The method of  claim 15 , wherein the method further comprises administering to the subject a taxane based agent.