Methods and compositions for the inhibition of stat5 in prostate cancer cells

Abstract

The present invention relates to compositions and methods for the treatment of prostate cancer. In certain embodiments, the invention relates to compositions and methods for the inhibition of prostate cancer cell growth, comprising inhibiting the activity of Stat5 in prostate cancer cells.

1 . A method of inhibiting prostate cancer cell growth, comprising inhibiting Stat5 activity in the prostate cancer cells.  
   
   
       2 . The method of  claim 1 , wherein Stat5 activity is inhibited by contacting the prostate cancer cells with an inhibitor of Stat5 activity.  
   
   
       3 . The method of  claim 2 , wherein the inhibitor Stat5 activity is selected from the group consisting of: a small molecule, an siRNA construct, an antisense construct, and an antibody.  
   
   
       4 . The method of  claim 3 , wherein the inhibitor of Stat5 activity is a nucleic acid, which encodes a protein that has dominant-negative Stat5 function.  
   
   
       5 . The method of  claim 4 , wherein the protein encoded is selected from the group consisting of: mutated Stat5a and mutated Stat5b.  
   
   
       6 . The method of  claim 5 , wherein the mutated Stat5a is Stat5aΔ713.  
   
   
       7 . The method of  claim 3 , wherein the agent that inhibits Stat5 activity is an antisense construct.  
   
   
       8 . The method of  claim 3 , wherein the agent that inhibits Stat5 activity is an siRNA construct.  
   
   
       9 . The method of  claim 8 , wherein the siRNA construct inhibits the activity of a Stat5 polypeptide.  
   
   
       10 . The method of  claim 9 , wherein the Stat5 polypeptide is selected from the group consisting of: Stat5a and Stat5b.  
   
   
       11 . The method of  claim 3 , wherein the siRNA construct is inhibits the expression of a Stat5 polypeptide.  
   
   
       12 . The method of  claim 11 , wherein the Stat5 polypeptide is selected from the group consisting of: Stat5a and Stat5b.  
   
   
       13 . The method of  claim 8 , wherein the siRNA construct comprises Stat5 nucleic acid.  
   
   
       14 . The method of  claim 13 , wherein the Stat5 nucleic acid is selected from the group consisting of: Stat5a nucleic acid and Stat5b nucleic acid.  
   
   
       15 . The method of  claim 2 , wherein the inhibitor of Stat5 inhibits of one or more Stat5 kinases.  
   
   
       16 . The method of  claim 15 , wherein the Stat5 kinase is selected from the group consisting of: Jak1, Jak2, Jak3, Tyk2, Src, Fyn, Yes, Lck, Hck, Blk, Fgr, and Lyn.  
   
   
       17 . The method of  claim 15 , wherein the inhibitor of Stat5 activity is a small molecule.  
   
   
       18 . The method of  claim 2 , wherein the inhibitor of Stat5 activity is a nucleic acid, which encodes a protein that has dominant negative Jak2 function.  
   
   
       19 . The method of  claim 2 , wherein the inhibitor of Stat5 activity inhibits of prolactin.  
   
   
       20 . The method of  claim 19 , wherein prolactin is inhibited by an antibody to a prolactin receptor.  
   
   
       21 . The method of  claim 2 , wherein the inhibitor of Stat5 activity in the prostate cancer cells results in prostate cancer cell death.  
   
   
       22 . A method of treating prostate cancer in a male in need of such treatment, comprising administering to the male an inhibitor of the activity of Stat5 in prostate cancer cells.  
   
   
       23 . The method of  claim 22 , wherein the prostate cancer cells are selected from the group consisting of: primary prostate cancer cells, advanced prostate cancer cells, and metastatic prostate cancer cells.  
   
   
       24 . The method of  claim 22 , wherein the inhibitor of the activity of Stat5 is selected from the group consisting of: a small molecule, an siRNA construct, an antisense construct, and an antibody.  
   
   
       25 . A method of diagnosing or aiding in the diagnosis of prostate cancer in a male, comprising: 
 (a) obtaining a sample of prostate tissue from a male; and    (b) determining whether activated Stat5 is present in cells of the prostate tissue sample,    wherein the presence of activated Stat5 is an indication of prostate cancer in the male.    
   
   
       26 . The method of  claim 25 , wherein the prostate cancer is primary prostate cancer, advanced prostate cancer, or metastatic prostate cancer.  
   
   
       27 . A method of treating prostate cancer in a male, comprising administering to a male in need of treatment thereof a therapeutically effective amount of an agent that inhibits the activity of Stat5 in prostate cancer cells, wherein the activity of Stat5 is inhibited in prostate cancer cells of the male.  
   
   
       28 . The method of  claim 27 , wherein the prostate cancer is primary prostate cancer, advanced prostate cancer, or metastatic prostate cancer.  
   
   
       29 . The method of  claim 27 , wherein the inhibitor of the activity of Stat5 is selected from the group consisting of: a small molecule, an siRNA construct, an antisense construct, and an antibody.  
   
   
       30 . The method of  claim 27 , wherein the inhibitor of Stat5 is a nucleic acid that encodes a protein that has dominant-negative Stat5 function.  
   
   
       31 . The method of  claim 30 , wherein the protein encoded is selected from the group consisting of: mutated Stat5a and mutated Stat5b.  
   
   
       32 . The method of  claim 31 , wherein the mutated Stat5a is Stat5aΔ713.  
   
   
       33 . The method of  claim 27 , wherein the agent that inhibits Stat5 activity is an antisense construct.  
   
   
       34 . The method of  claim 27 , wherein the agent that inhibits Stat5 activity is an siRNA construct.  
   
   
       35 . The method of  claim 34 , wherein the siRNA construct inhibits activity of a Stat5 polypeptide.  
   
   
       36 . The method of  claim 35 , wherein the Stat5 polypeptide is selected from the group consisting of: Stat5a and Stat5b.  
   
   
       37 . The method of  claim 34 , wherein the siRNA construct inhibits the expression of a Stat5 polypeptide.  
   
   
       38 . The method of  claim 36 , wherein the Stat5 polypeptide is selected from the group consisting of: Stat5a and Stat5b.  
   
   
       39 . The method of  claim 34 , wherein the siRNA construct comprises Stat5 nucleic acid.  
   
   
       40 . The method of  claim 39 , wherein the Stat5 nucleic acid is selected from the group consisting of: Stat5a nucleic acid and Stat5b nucleic acid.  
   
   
       41 . The method of  claim 27 , wherein Stat5 activity is reduced through the inhibition of one or more Stat5 kinases.  
   
   
       42 . The method of  claim 41 , wherein the Stat5 kinase is selected from the group consisting of: Jak1, Jak2, Jak3, Tyk2, Src, Fyn, Yes, Lck, Hck, Blk, Fgr, and Lyn.  
   
   
       43 . The method of  claim 41 , wherein the inhibitor of one or more Stat5 kinases is a small molecule.  
   
   
       44 . The method of  claim 27 , wherein the inhibitor of Stat5 is a nucleic acid, which encodes a protein that has dominant negative Jak2 function.  
   
   
       45 . The method of  claim 27 , wherein Stat5 activity is reduced through inhibition of prolactin.  
   
   
       46 . The method of  claim 45 , wherein prolactin is inhibited by an antibody to a prolactin receptor.  
   
   
       47 . The method of  claim 27 , wherein inhibition of the activity of Stat5 in prostate cancer cells of the male results in prostate cancer cell death.  
   
   
       48 . The method of  claim 25 , wherein the presence of activated Stat5 in (b) is detected by a method selected from the group consisting of: 
 immunohistochemistry, immunocytochemistry and DNA-binding assays.    
   
   
       49 . The method of  claim 25 , wherein the activated Stat5 in (b) is nuclear Stat5.  
   
   
       50 . A method for identifying an agent that inhibits Stat5 activity in prostate cancer cells, comprising: 
 (a) contacting a prostate cancer cell or tissue sample comprising prostate cancer cells with a candidate agent; and    (b) determining the effect of the agent in (a) on the Stat5 activity wherein if Stat5 activity determined in (b) is less than Stat5 activity in an appropriate control sample, an inhibitor of Stat5 activity is identified.    
   
   
       51 . A diagnostic method for predicting responsiveness to Stat5 inhibition therapy for treatment of prostate cancer, comprising: 
 (a) obtaining a sample of prostate tissue from a male in need of treatment for prostate cancer, and    (b) determining whether activated Stat5 is present in cells in the prostate tissue sample,    wherein if the presence of activated Stat5 is determined, it is predictive of responsiveness to Stat5 inhibition therapy for treatment of prostate cancer.    
   
   
       52 . The method of  claim 51 , wherein the prostate cancer is primary prostate cancer, advanced prostate cancer, or metastatic prostate cancer.  
   
   
       53 . A use of an inhibitor of Stat5 activity to prepare a medicament to inhibit prostate cancer cell growth.  
   
   
       54 . A use of an inhibitor of Stat5 activity to prepare a medicament to treat prostate cancer in a male in need of treatment thereof.