Use of an rxr agonist in treating her2+ cancers

Abstract

The present specification provides combinations of active agents for the improved treatment of Her2+ cancers and associated methods of treatments. The combinations comprise and RXR agonist and a Her2-targeted therapeutic agent and may optionally further comprise thyroid hormone.

1 . A method of treating a patient with Her2 +  breast cancer comprising administering a RXR agonist of Formula I, 
       
         
           
           
               
               
           
         
         wherein R is H, or lower alkyl of 1 to 6 carbons; or a pharmaceutically-acceptable salt thereof, to the patient, 
         wherein the patient is receiving a Her2-targeted therapeutic agent. 
       
     
     
         2 . The method of  claim 1 , wherein the Her2-targeted therapeutic agent consists of means for therapeutically targeting Her2. 
     
     
         3 . The method of  claim 2 , wherein the means for therapeutically targeting Her2 consists of means for inhibiting Her2 +  tumor cell proliferation. 
     
     
         4 . The method of  claim 2 , wherein the means for therapeutically targeting Her2 consists of small molecule means for inhibiting Her2 kinase activity. 
     
     
         5 . A method of treating a patient with Her2 +  breast cancer undergoing treatment with a Her2-targeted therapeutic agent, wherein there is evidence of therapeutic effect that is less than a complete response, comprising continuing treatment with the Her2 kinase inhibitor and initiating treatment with a RXR agonist of Formula I, 
       
         
           
           
               
               
           
         
         wherein R is H, or lower alkyl of 1 to 6 carbons; or a pharmaceutically-acceptable salt thereof. 
       
     
     
         6 . The method of  claim 5 , wherein the Her2-targeted therapeutic agent consists of means for therapeutically targeting Her2. 
     
     
         7 . The method of  claim 6 , wherein the means for therapeutically targeting Her2 consists of means for inhibiting Her2 +  tumor cell proliferation. 
     
     
         8 . The method of  claim 6 , wherein the means for therapeutically targeting Her2 consists of small molecule means for inhibiting Her2 kinase activity. 
     
     
         9 . A method of treating a patient with Her2 +  breast cancer comprising administering means for activating RXR/Nurr1 heterodimeric receptors, wherein the patient is receiving a Her2-targeted therapeutic agent. 
     
     
         10 . The method of  claim 9 , wherein the Her2-targeted therapeutic agent comprises a therapeutic anti-Her2 antibody. 
     
     
         11 . The method of  claim 9 , wherein the Her2-targeted therapeutic agent is a small organic molecule inhibitor of Her2 kinase activity. 
     
     
         12 . The method of  claim 1 , further comprising administering thyroid hormone in conjunction with the RXR agonist. 
     
     
         13 . The method of  claim 5 , further comprising administering thyroid hormone in conjunction with the RXR agonist. 
     
     
         14 . The method of  claim 9 , further comprising administering thyroid hormone in conjunction with the means for activating RXR/Nurr1 heterodimeric receptors. 
     
     
         15 . The method of  claim 1 , wherein the inhibition of tumor cell growth by the combination of the Her2-targeted therapeutic and the RXR agonist is greater than additive effects of each of the Her2-targeted therapeutic and the RXR agonist alone. 
     
     
         16 . The method of  claim 5 , wherein the inhibition of tumor cell growth by the combination of the Her2-targeted therapeutic and the RXR agonist is greater than additive effects of each of the Her2-targeted therapeutic and the RXR agonist alone. 
     
     
         17 . The method of  claim 9 , wherein the inhibition of tumor cell growth by the combination of the Her2-targeted therapeutic and the means for activating RXR/Nurr1 heterodimeric receptors is greater than additive effects of each of the Her2-targeted therapeutic and the means for activating RXR/Nurr1 heterodimeric receptors alone.