Method of cancer treatment by p53 protein control

Abstract

Method of cancer treatment by controlling cellular p53 protein levels. The invention concerns, in particular, the use of a compound capable of modulating calpaine activity.

1 . Use of a compound capable of modulating the activity of calpain for the preparation of a pharmaceutical composition for the treatment of cancer.  
     
     
         2 . Use according to  claim 1 , characterized in that the compound is a protein or a polypeptide which is an inhibitor of the activity of calpain, or a nucleic acid sequence encoding such a polypeptide or protein.  
     
     
         3 . Use according to  claim 2 , characterized in that the compound is a protein or a polypeptide which is a specific inhibitor of the activity of calpain on the wild-type p53 protein, or a nucleic acid sequence encoding such a polypeptide or protein.  
     
     
         4 . Use according to  claim 2  or  3 , characterized in that the nucleic acid is part of a vector.  
     
     
         5 . Use according to  claim 4 , characterized in that the nucleic acid is part of a viral vector, chosen from adenoviruses, retroviruses and adeno-associated viruses.  
     
     
         6 . Use according to  claim 4 , characterized in that the nucleic acid is part of a lipid liposomal vector.  
     
     
         7 . Use according to one of the preceding claims, characterized in that the compound is a nucleic acid encoding all or part of calpastatin.  
     
     
         8 . Use according to  claim 7 , characterized in that the nucleic acid comprises all or part of the sequence SEQ ID No. 1 or a derivative thereof.  
     
     
         9 . Use according to  claim 8 , characterized in that the nucleic acid is chosen from the sequences SEQ ID No. 1 and 2.  
     
     
         10 . Use according to  claim 8 , characterized in that the nucleic acid is chosen from the derivatives of the sequences SEQ ID No. 1 or 2 encoding specific inhibitors of the degradation of the wild-type p53 protein.  
     
     
         11 . Use according to one of  claims 1  to  6 , characterized in that the compound is a derivative of calpain capable of specifically degrading the mutated p53 proteins.  
     
     
         12 . Viral vector comprising a nucleic acid sequence encoding a protein or a polypeptide which is an inhibitor of the activity of calpain.  
     
     
         13 . Vector according to  claim 12 , characterized in that it is chosen from the adenoviruses, retroviruses and adeno-associated viruses.  
     
     
         14 . Vector according to either of claims  12  or  13 , characterized in that it comprises a sequence encoding all or part of calpastatin.  
     
     
         15 . Vector according to  claim 12 , characterized in that it comprises a sequence encoding a derivative of calpain capable of specifically degrading the mutated p53 proteins.  
     
     
         16 . Pharmaceutical composition comprising a nucleic acid sequence encoding all or part of calpastatin or a derivative of calpain capable of specifically degrading the mutated p53 proteins.  
     
     
         17 . Composition according to  claim 16 , formulated for inttra-tumour administration.