Novel methods of diagnosing colorectal cancer, compositions, and methods of screening for colorectal cancer modulators

Abstract

Described herein are methods that can be used for diagnosis and prognosis of colorectal cancer. Also described herein are methods that can be used to screen candidate bioactive agents for the ability to modulate colorectal cancer. Additionally, methods and molecular targets (genes and their products) for therapeutic intervention in colorectal cancer are described.

We claim:  
     
         1 . A method of screening drug candidates comprising: 
 a) providing a cell that expresses an expression profile gene encoding CJA8 or fragment thereof;    b) adding a drug candidate to said cell; and    c) determining the effect of said drug candidate on the expression of said expression profile gene.    
     
     
         2 . A method according to  claim 1  wherein said determining comprises comparing the level of expression in the absence of said drug candidate to the level of expression in the presence of said drug candidate.  
     
     
         3 . A method of screening for a bioactive agent capable of binding to CJA8 or a fragment thereof, said method comprising: 
 a) combining said CJA8 or a fragment thereof and a candidate bioactive agent; and    b) determining the binding of said candidate agent to said CJA8 or a fragment thereof.    
     
     
         4 . A method for screening for a bioactive agent capable of modulating the activity of CJA8, said method comprising: 
 a) combining CJA8 and a candidate bioactive agent; and    b) determining the effect of said candidate agent on the bioactivity of CJA8.    
     
     
         5 . A method of evaluating the effect of a candidate colorectal cancer drug comprising: 
 a) administering said drug to a patient;    b) removing a cell sample from said patient; and    c) determining the expression of a gene encoding CJA8 or fragment thereof.    
     
     
         6 . A method according to  claim 5  further comprising comparing said expression profile to an expression profile of a healthy individual.  
     
     
         7 . A method of diagnosing colorectal cancer comprising: 
 a) determining the expression of a gene encoding CJA8 or a fragment thereof in a first colon tissue of a first individual; and    b) comparing said expression of said gene(s) from a second normal colon tissue from said first individual or a second unaffected individual;    wherein a difference in said expression indicates that the first individual has colorectal cancer.    
     
     
         8 . An antibody which specifically binds to CJA8 or a fragment thereof.  
     
     
         9 . The antibody of  claim 8 , wherein said antibody is a monoclonal antibody.  
     
     
         10 . The antibody of  claim 8 , wherein said antibody is a humanized antibody.  
     
     
         11 . The antibody of  claim 8 , wherein said antibody is an antibody fragment.  
     
     
         12 . The antibody of  claim 8 , wherein said antibody modulates the bioactivity of CJA8.  
     
     
         13 . The antibody of  claim 12 , wherein said antibody is capable of inhibiting the bioactivity or neutralizing the effect of CJA8.  
     
     
         14 . A method for screening for a bioactive agent capable of interfering with the binding of CJA8 or a fragment thereof and an antibody which binds to CJA8 or fragment thereof, said method comprising: 
 a) combining CJA8 or fragment thereof, a candidate bioactive agent and an antibody which binds to CJA8 or fragment thereof; and    b) determining the binding of CJA8 or fragment thereof and said antibody.    
     
     
         15 . A method according to  claim 14 , wherein said antibody is capable of inhibiting or neutralizing the bioactivity of CJA8.  
     
     
         16 . A method for inhibiting the activity of CJA8, said method comprising binding an inhibitor to CJA8.  
     
     
         17 . A method according to  claim 16  wherein said inhibitor is an antibody.  
     
     
         18 . A method of neutralizing the effect of CJA8 or a fragment thereof, comprising contacting an agent specific for said CJA8 or fragment thereof with said CJA8 or fragment thereof in an amount sufficient to effect neutralization.  
     
     
         19 . A method of treating colorectal cancer comprising administering to a patient an inhibitor of CJA8.  
     
     
         20 . A method according to  claim 19  wherein said inhibitor is an antibody.  
     
     
         21 . A method for localizing a therapeutic moiety to colorectal cancer tissue comprising exposing said tissue to an antibody to CJA8 or fragment thereof conjugated to said therapeutic moiety.  
     
     
         22 . The method of  claim 21 , wherein said therapeutic moiety is a cytotoxic agent.  
     
     
         23 . The method of  claim 21 , wherein said therapeutic moiety is a radioisotope.  
     
     
         24 . A method of treating colorectal cancer comprising administering to an individual having said colorectal cancer an antibody to CJA8 or fragment thereof conjugated to a therapeutic moiety.  
     
     
         25 . The method of  claim 24 , wherein said therapeutic moiety is a cytotoxic agent.  
     
     
         26  The method of  claim 24 , wherein said therapeutic moiety is a radioisotope.  
     
     
         27 . A method for inhibiting colorectal cancer in a cell, wherein said method comprises administering to a cell a composition comprising antisense molecules to a nucleic acid of FIG. 1.  
     
     
         28 . A biochip comprising one or more nucleic acid segments encoding CJA8 or a fragment thereof, wherein said biochip comprises fewer than 1000 nucleic acid probes.  
     
     
         29 . A method of eliciting an immune response in an individual, said method comprising administering to said individual a composition comprising CJA8 or a fragment thereof.  
     
     
         30 . A method of eliciting an immune response in an individual, said method comprising administering to said individual a composition comprising a nucleic acid encoding CJA8 or a fragment thereof.  
     
     
         31 . A method for determining the prognosis of an individual with colorectal cancer comprising determining the level of CJA8 in a sample, wherein a high level of CJA8 indicates a poor prognosis.