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, and administering to the subject an effective amount of an anti-hormonal agent, wherein said composition comprises one or more ingredients selected from the group consisting of polynucleotides encoding an siRNA for PAX2, polynucleotides that inhibits binding of PAX2 to DEFB1 promoter, antagonists of angiotensin II, antagonists of angiotensin-converting enzyme (ACE), antagonists of mitogen-activated protein kinase (MEK), antagonists of extracellular signal-regulated kinase 1,2 (ERK1,2), antagonists of signal transducer, and blockers of the RAS signaling pathway. 
     
     
         2 . The method of  claim 1 , wherein the breast condition is breast cancer or mammary intraepithelial neoplasia (MIN). 
     
     
         3 - 13 . (canceled) 
     
     
         14 . The method of  claim 1 , 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 an antagonist selected from the group consisting of antagonists of angiotensin II, antagonists of angiotensin-converting enzyme (ACE), antagonists of mitogen-activated protein kinase (MEK), antagonists of extracellular signal-regulated kinase 1,2 (ERK1,2), and antagonists of signal transducer. 
     
     
         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.