Targeting pax2 for the treatment of breast cancer

Abstract

The present application provides methods of prevention and/or treatment of breast cancer in a subject by inhibiting expression of PAX2. In the cancer treatment methods disclosed, the method of inhibiting expression of PAX2 can be by administration of a nucleic acid encoding an siRNA for PAX2. A method of treating cancer in a subject by administering DEFB1 is also provided. Similarly, provided is a method of treating cancer in a subject by increasing expression of DEFB1 in the subject.

1 . A method for treating a breast condition in a subject, comprising administering to the subject, an effective amount of a composition that inhibits PAX2 expression and/or PAX2 activity,
 wherein said composition comprises antagonists of mitogen-activated protein kinase (MEK).   
     
     
         2 . The method of  claim 1 , wherein the breast condition is breast cancer or mammary intraepithelial neoplasia (MIN). 
     
     
         3 - 8 . (canceled) 
     
     
         9 . The method of  claim 1 , wherein said composition comprises U0126 or PD98059. 
     
     
         10 - 12 . (canceled) 
     
     
         13 . The method of  claim 1 , further comprising the step of:
 administering to the subject an effective amount of an anti-hormonal agent.   
     
     
         14 . The method of  claim 13 , wherein the anti-hormonal agent is Tamoxifen. 
     
     
         15 . The method of  claim 1 , further comprising the step of:
 administering to the subject an effective amount of an anti-ERBB-2 agent.   
     
     
         16 . The method of  claim 15 , wherein the said anti-ERBB-2 agent is Herceptin. 
     
     
         17 . The method of  claim 1 , further comprising the step of:
 administering to the subject an effective amount of an anti-Her-2 agent.   
     
     
         18 . The method of  claim 17 , wherein the anti-Her-2 agent is Trastuzumab. 
     
     
         19 . The method of  claim 1 , further comprising the step of:
 administering to the subject an effective amount of an anti-AIB-1/SRC-3 agent.   
     
     
         20 . The method of  claim 1 , wherein said composition further comprises on or more agents selected from the group consisting of anti-hormonal agents, anti-ERBB-2 agents, anti-Her-2 agents, and anti-AIB-1/SRC-3 agent. 
     
     
         21 . A method for treating a breast condition in a subject, comprising:
 (a) determining the PAX2-to-DEFB1 expression ratio in a diseased breast tissue from said subject;   (b) determining the ER/PR status of said diseased breast tissue from said subject; and   (c) based on the results of (a) and (b), administering to a breast tissue of said subject, a first composition that (1) inhibits PAX2 expression or PAX2 activity, (2) expresses DEFB1 or (3) inhibits PAX2 expression or PAX2 activity and expresses DEFB1.   
     
     
         22 . The method of  claim 21 , wherein said breast condition is breast cancer or MIN. 
     
     
         23 - 26 . (canceled) 
     
     
         27 . The method of  claim 21 , wherein said first composition comprises antagonists of mitogen-activated protein kinase (MEK). 
     
     
         28 . (canceled) 
     
     
         29 . The method of  claim 21 , wherein said first composition is an anti-PAX2 agent conjugated to an antibody, a receptor or a ligand to target tumor tissue in said subject. 
     
     
         30 . (canceled) 
     
     
         31 . The method of  claim 21 , wherein the step (c) further comprises administering a second composition comprising an anti-hormonal agent. 
     
     
         32 . The method of  claim 31 , wherein the anti-hormonal agent is Tamoxifen. 
     
     
         33 . The method of  claim 21 , wherein the step (c) further comprises administering a second composition comprising an anti-ERBB-2 agent. 
     
     
         34 . The method of  claim 33 , wherein the anti-anti-ERBB-2 agent is Herceptin. 
     
     
         35 . The method of  claim 21 , wherein the step (c) further comprises administering a second composition comprising an anti-Her-2 agent. 
     
     
         36 . The method of  claim 35 , wherein the anti-anti-Her-2 agent is Trastuzumab 
     
     
         37 . The method of  claim 21 , wherein the step (c) further comprises administering a second a second composition comprising an anti-AIB-1/SRC-3 agent.