Compounds and methods for modulating cell-adhesion mediated drug resistance

Abstract

Peptides and methods of their use for inhibiting drug and radiation-therapy resistance in cancerous cells in which efficacy of chemotherapy and/or radiotherapy of a patient is enhanced by administration of an effective amount of a peptide that inhibits cell adhesion mediated drug resistance (CAM-DR). Preferably, the peptide comprises D-amino acids having the sequence: kmviywkag (RZ-3) or is a variant or modified version thereof. The peptide is preferably administered to the patient prior to chemotherapy and/or radiation therapy. Inhibition of cell adhesion mediated drug resistance (CAM-DR) by RZ-3 in multiple myeloma cells is disclosed.

1 . A method for inhibiting cell adhesion mediated drug resistance in a patient in need thereof, comprising: 
 administering to said patient an effective amount of a peptide that inhibits cell adhesion mediated drug resistance.    
     
     
         2 . The method of  claim 1 , wherein said peptide comprises at least one D-amino acid.  
     
     
         3 . The method of  claim 1 , wherein said peptide comprises the amino acid sequence: 
 kmviywkag    or a variant thereof.    
     
     
         4 . The method of  claim 2 , wherein said peptide comprises RZ-3.  
     
     
         5 . The method of  claim 4 , wherein said peptide is RZ-3.  
     
     
         6 . A method for enhancing the efficacy of chemotherapy or radiation therapy in a patient in need thereof, comprising: 
 administering an effective amount of a peptide, wherein said peptide inhibits cell adhesion mediated drug resistance in said patient; and    administering to said patient chemotherapy, radiation therapy, or both;    whereby the efficacy of said therapy is enhanced.    
     
     
         7 . The method of  claim 6 , wherein said peptide comprises at least one D-amino acid.  
     
     
         8 . The method of  claim 6 , wherein said peptide comprises the amino acid sequence: 
 kmviywkag    or a variant thereof.    
     
     
         9 . The method of  claim 7 , wherein said peptide comprises RZ-3.  
     
     
         10 . The method of  claim 9 , wherein said peptide is RZ-3.  
     
     
         11 . A method for treating cancer in a patient in need thereof, comprising: 
 administering to said patient an effective amount of a peptide, wherein said peptide inhibits cell adhesion mediated drug resistance in said patient; and    administering chemotherapy, radiation therapy or both.    
     
     
         12 . The method of  claim 1   1 , wherein said peptide comprises at least one D-amino acid.  
     
     
         13 . The method of  claim 11 , wherein said peptide comprises the amino acid sequence: 
 kmviywkag    or a variant thereof.    
     
     
         14 . The method of  claim 12 , wherein said peptide comprises RZ-3.  
     
     
         15 . The method of  claim 14 , wherein said peptide is RZ-3.  
     
     
         16 . The method of  claim 1   1 , wherein said cancer is a myeloma.  
     
     
         17 . The method of  claim 1   1 , wherein said cancer is multiple myeloma.  
     
     
         18 . A peptide comprising D-amino acids and having a sequence: 
 kmviywkag    or a variant thereof.    
     
     
         19 . A pharmaceutical composition comprising the peptide RZ-3, or a pharmaceutically acceptable salt thereof, in a pharmaceutically acceptable carrier.