Treatment of cancer

Abstract

The present invention relates to agents for use in treating cancer. The agent to be used is an antagonist of Dsg2, wherein said antagonist modulates the function of the amino acid sequence: TQDVFVGSVEELSAAHTLVMKINATDADEPNTLNSKISYR (SEQ ID NO:1), or a fragment or variant thereof, of the EC2 domain of Dsg2. Also included in the invention are specific polypeptides and pharmaceutical preparations. Also included in the invention is a method of screening for antagonists of Dsg2, wherein said antagonist modulates the function of the amino acid sequence: TQDVFVGS VEELSAAHTLVMKINATDADEPNTLNSKISYR (SEQ ID NO: 1), or a fragment or variant thereof, of the EC2 domain of Dsg2.

1 - 23 . (canceled) 
     
     
         24 . A method of treating cancer comprising administering to a subject a therapeutically effective quantity of an antagonist of desmoglein 2 (Dsg2), wherein said antagonist modulates the function of the amino acid sequence: TQDVFVGSVEELSAAHTLVMKINATDADEPNTLNSKISYR (SEQ ID NO:1), or a fragment or variant thereof, of the EC2 domain of Dsg2 and wherein the antagonist is a peptide or peptidomimetic. 
     
     
         25 . The method of  claim 24  wherein the antagonist reduces the epithelial-mesenchymal transition (EMT) promoting function of Dsg2. 
     
     
         26 . The method of  claim 24  wherein the antagonist specifically binds to the amino acid sequence of SEQ ID NO:1. 
     
     
         27 . The method of  claim 24  wherein the peptide or peptidomimetic includes some or all of the amino acid sequence SEQ ID NO:1, or amino acid derivatives or analogues thereof. 
     
     
         28 . The method of  claim 27  wherein the peptide comprises the amino acid sequence: TQDVFVGSVEELSAAHTLVMKINATDADEPNTLNSKISYR (SEQ ID NO:1), KINATDADEPNTLNSKISYR (SEQ ID NO:6) or EELSAAHTLV (SEQ ID NO:7) or amino acid derivatives or analogues thereof. 
     
     
         29 . The method of  claim 24  wherein the antagonist reduces the cell metastasis and/or cell invasion promoting function of Dsg2. 
     
     
         30 . The method of  claim 24 , wherein the cancer is prostate cancer, breast cancer or skin cancer. 
     
     
         31 . A method of treating cancer comprising administering to a subject a therapeutically effective quantity of an antagonist of desmoglein 2 (Dsg2), wherein said antagonist is a Dsg2 polypeptide or a fragment or variant thereof, wherein said polypeptide has one or more amino acid residue substitutions, inversions and/or deletions within the sequence TQDVFVGSVEELSAAHTLVMKINATDADEPNTLNSKISYR (SEQ ID NO:1), or a fragment or variant thereof, of the EC2 domain of Dsg2. 
     
     
         32 . The method of  claim 31  wherein the polypeptide comprises the amino acid sequence of SEQ ID NO:9. 
     
     
         33 . A method of treating cancer comprising administering to a subject a therapeutically effective quantity of an antagonist of desmoglein 2 (Dsg2), wherein said antagonist is a polypeptide comprising the amino acid sequence of SEQ ID NO:2 or a fragment or variant thereof, wherein said polypeptide has one or more amino acid residue replacements, inversions and/or deletions within the sequence TQDVFVGSVEELSAAHTLVMKINATDADEPNTLNSKISYR (SEQ ID NO:1) or a fragment or variant thereof of the EC2 domain of Dsg2. 
     
     
         34 . The method of  claim 33  wherein the polypeptide comprises the amino acid sequence of SEQ ID NO:9.