Phenotypic reversion of pancreatic carcinoma cells

Abstract

The present invention provides peptides (including analogs and derivatives thereof) corresponding to residues 96-110 and 35-47 of ras-p21, which peptides have attached thereto a membrane-penetrating leader sequence. The subject peptides, analogs and derivatives thereof are useful in treatment of cancers and have been shown to induce phenotypic reversion of pancreatic cancer cells to non-cancerous cells. Pharmaceutical compositions comprising one or more subject peptides are also provided by the present invention. The present invention further provides replication incompetent Adenovirus (AdV) vectors comprising a promoter sequence and a nucleotide sequence encoding a subject peptide. Methods of treating cancer by administering one or more subject peptides, pharmaceutical compositions, and/or AdV vectors are also provided.

1 . A replication incompetent Adenovirus (AdV) vector comprising a promoter sequence operably linked to a nucleotide sequence encoding a peptide, wherein the peptide comprises at least about ten contiguous amino acids of the amino acid sequence: YREQIKRVKDSDDVP (SEQ ID NO: 1), or an analog or derivative thereof. 
     
     
         2 . A replication incompetent Adenovirus (AdV) vector comprising a promoter sequence operably linked to a nucleotide sequence encoding a peptide, wherein the peptide comprises at least about ten contiguous amino acids of the amino acid sequence: TIEDSYRKQVVID (SEQ ID NO: 2), or an analog or derivative thereof. 
     
     
         3 . A method of treating a patient suffering from cancer, said method comprising administering to the patient, a therapeutically effective amount of the AdV vector of  claim 1 . 
     
     
         4 . A method of treating a patient suffering from cancer, said method comprising administering to the patient, a therapeutically effective amount of the AdV vector of  claim 2 . 
     
     
         5 . A method of inducing phenotypic reversion of cancerous cells to non-cancerous cells in a subject, said method comprising administering to the subject, a therapeutically effective amount of the AdV vector of  claim 1 . 
     
     
         6 . A method of inducing phenotypic reversion of cancerous cells to non-cancerous cells in a subject, said method comprising administering to the subject, a therapeutically effective amount of the AdV vector of  claim 2 . 
     
     
         7 . The method of  claim 5  wherein the cancerous cells are colon cancer cells, pancreatic cancer cells, non-small cell carcinoma of the lung, gastric cancer cells, bladder cancer cells or mesothelioma cells. 
     
     
         8 . The method of  claim 6  wherein the cancerous cells are colon cancer cells, pancreatic cancer cells, non-small cell carcinoma of the lung, gastric cancer cells, bladder cancer cells or mesothelioma cells.