Activin-actriia antagonists and uses for treating or preventing breast cancer

Abstract

In certain aspects, the present invention provides compositions and methods for treating or preventing breast cancer in humans.

1 . A method for treating or preventing metastatic breast cancer in a human patient, the method comprising administering to the patient an effective amount of an ActRIIa-Fc fusion protein, wherein the ActRIIa-Fc fusion protein comprises a polypeptide selected from the group consisting of:
 a) a polypeptide comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO:2,   b) a polypeptide comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO:3,   c) a polypeptide comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO:7, and   d) a polypeptide comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO:12.   
     
     
         2 - 3 . (canceled) 
     
     
         4 . The method of  claim 1 , wherein said ActRIIa-Fc fusion protein comprises one or more modified amino acid residues selected from: a glycosylated amino acid, a PEGylated amino acid, a farnesylated amino acid, an acetylated amino acid, a biotinylated amino acid, and an amino acid conjugated to a lipid moiety. 
     
     
         5 . The method of  claim 1 , wherein the ActRIIa-Fc fusion protein comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:3. 
     
     
         6 . The method of  claim 1 , wherein the ActRIIa-Fc fusion protein comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:2. 
     
     
         7 . The method of  claim 1 , wherein the ActRIIa-Fc fusion protein comprises the amino acid sequence of SEQ ID NO:3. 
     
     
         8 . The method of  claim 1 , wherein the ActRIIa-Fc fusion protein comprises the amino acid sequence of SEQ ID NO:2. 
     
     
         9 - 20 . (canceled) 
     
     
         21 . The method of  claim 1 , further comprising administering a radiation therapy, endocrine therapy or cytotoxic agent to the human patient. 
     
     
         22 - 39 . (canceled) 
     
     
         40 . The method of  claim 1 , wherein the ActRIIa-Fc fusion protein comprises an amino acid sequence that is at least 95% identical to SEQ ID NO:7. 
     
     
         41 . The method of  claim 1 , wherein the ActRIIa-Fc fusion protein comprises the amino acid sequence of SEQ ID NO:7. 
     
     
         42 . The method of  claim 1 , wherein the ActRIIa-Fc fusion protein comprises an amino acid sequence that is at least 95% identical to SEQ ID NO:12. 
     
     
         43 . The method of  claim 1 , wherein the ActRIIa-Fc fusion protein comprises the amino acid sequence of SEQ ID NO:12. 
     
     
         44 . The method of  claim 1 , wherein the patient is at risk for developing metastatic breast cancer. 
     
     
         45 . The method of  claim 1 , wherein the patient has a primary breast cancer tumor or proliferative lesion of the breast, and wherein the ActRIIa-Fc fusion protein is administered to the patient prior to the development of metastatic lesions. 
     
     
         46 . The method of  claim 1 , wherein the patient has a primary breast cancer tumor or proliferative lesion of the breast, and wherein the ActRIIa-Fc fusion protein is administered to the patient prior to metastatic spread of cancer cells to the bone. 
     
     
         47 . The method of  claim 1 , wherein the ActRIIa-Fc fusion protein binds to activin A and/or GDF11. 
     
     
         48 . The method of  claim 47 , wherein the ActRIIa-Fc fusion protein binds to activin. 
     
     
         49 . The method of  claim 48 , wherein the ActRIIa-Fc fusion protein binds to activin A. 
     
     
         50 . The method of  claim 48 , wherein the ActRIIa-Fc fusion protein binds to activin B. 
     
     
         51 . The method of  claim 47 , wherein the ActRIIa-Fc fusion protein binds to GDF11.