Methods and pharmaceutical compositions for treatment of anti-estrogen resistant breast cancer using RXR modulators

Abstract

Methods and compositions for the treatment of anti-estrogen resistant breast cancer using retinoid compounds that are modulators of Retinoid X Receptors are provided.

1 . A method for treating a host having anti-estrogen resistant breast cancer, comprising administering to the host a composition comprising a pharmaceutically effective amount of a Retinoid X Receptor (RXR) modulator.  
   
   
       2 . The method of  claim 1 , wherein the RXR modulator is an RXR selective modulator.  
   
   
       3 . The method of  claim 2 , wherein the RXR selective modulator is selected from among LGD1069, LGD100268 and LGD100324 and pharmaceutically acceptable salts thereof.  
   
   
       4 . The method of  claim 2 , wherein the modulator selectively activates one or more RXRs in preference to all of RAR isoforms α, β and γ.  
   
   
       5 . A pharmaceutical composition for the treatment of a host having anti- estrogen resistant breast cancer, comprising: 
 (a) a pharmaceutically effective amount of an RXR modulator; and    (b) a pharmaceutically acceptable carrier.    
   
   
       6 . The pharmaceutical composition of  claim 5 , wherein the RXR modulator is an RXR selective modulator.  
   
   
       7 . The pharmaceutical composition of  claim 5 , wherein the RXR modulator is selected from among LGD1069, LGD100268, and LGD100324 and pharmaceutically acceptable salts thereof.  
   
   
       8 . The pharmaceutical composition of  claim 6 , wherein the modulator selectively activates one or more RXRs in preference to all of RAR isoforms α, β and γ.  
   
   
       9 . A method for inhibiting the growth of anti-estrogen resistant breast cancer in a tissue, comprising contacting the tissue with an effective amount of an RXR selective modulator.  
   
   
       10 . The method of  claim 9 , wherein the modulator selectively activates one or more RXRs in preference to all of RAR isoforms α, β and γ.  
   
   
       11 . A method for treating a host having estrogen receptor negative status breast cancer, comprising administering to the host a composition comprising a pharmaceutically effective amount of an RXR selective modulator.  
   
   
       12 . The method of  claim 11 , wherein the estrogen receptor negative status is tamoxifen induced.  
   
   
       13 . The method of  claim 11 , wherein the status is initially present in the cancer.  
   
   
       14 . The method of  claim 11 , wherein the modulator selectively activates one or more RXRs in preference to all of RAR isoforms α, β and γ.  
   
   
       15 . The method of  claim 1 , wherein the anti-estrogen resistant breast cancer is tamoxifen-resistant breast cancer.  
   
   
       16 . The method of  claim 15 , wherein the RXR selective modulator is selected from among LGD1069, LGD100268, and LGD100324 and pharmaceutically acceptable salts thereof.