Predicting cancer progression

Abstract

The present invention involves early prediction of progression of a cancer disease in patients treated for cancer. According to the invention the binding response level of an immunoreactive material (IM) comprising thymidine kinase 1 (TK1) protein is determined in a body fluid sample of a patient and the likelihood of progress of the cancer disease is estimated based directly on this determined IM binding response level. Those patients that run a risk of cancer progress and tumor relapse 1-15 years after the cancer treatment may be identified directly by the IM binding response level according to the invention within a few months following initiation of the treatment.

1 . A method of predicting progression of a cancer disease in a subject treated for said cancer disease comprising the steps of: 
 determining a binding response level of an immunoreactive material (IM) comprising enzymatically active and inactive thymidine kinase 1 (TK1) protein in said subject; and    estimating a likelihood of progress of said cancer disease based on said determined IM binding response level.    
     
     
         2 . A method of generating decision support information for progression of a cancer disease in a subject treated for said cancer disease comprising the step of generating said decision support information based on a binding response level of an immunoreactive material (IM) comprising enzymatically active and inactive thymidine kinase 1 (TK1) protein determined in a sample from said subject.  
     
     
         3 . The method according to  claim 1 , wherein said TK1 protein comprising immunoreactive material is selected from at least one of: 
 TK1 protein; and    a complex of TK1 protein and another molecule.    
     
     
         4 . The method according to  claim 1 , further comprising the steps of: 
 determining a first IM binding response level in said subject no later than one month after initiation of said cancer treatment; and    determining a second IM binding response level in said subject after initiation of said cancer treatment, wherein said estimating step comprises estimating said likelihood of progress of said cancer disease based on said first and second IM binding response level.    
     
     
         5 . The method according to  claim 2 , further comprising the steps of: 
 determining a first IM binding response level in said subject no later than one month after initiation of said cancer treatment; and    determining a second IM binding response level in said subject after initiation of said cancer treatment, wherein said generating step comprises generating said decision support information based said first and second IM binding response levels.    
     
     
         6 . The method according to  claim 4 , further comprising predicting progress of said cancer disease if a ratio of said second IM binding response level and said first IM binding response level exceeds one.  
     
     
         7 . The method according to  claim 4 , wherein said first IM binding response level is determined in said subject before initiation of said cancer treatment.  
     
     
         8 . The method according to  claim 4 , wherein said second IM binding response level is determined in said subject within the first six months following initiation of said cancer treatment.  
     
     
         9 . The method according to  claim 1 , further comprising mapping said determined IM binding response level to a concentration level of said TK1 protein comprising immunoreactive material, and said estimating step comprises estimating said likelihood of progress of said cancer disease based on said determined concentration level.  
     
     
         10 . The method according to  claim 2 , further comprising mapping said determined IM binding response level to a concentration level of said TK1 protein comprising immunoreactive material, and said generating step comprises generating said decision support information based on said determined concentration level.  
     
     
         11 . The method according to  claim 9 , wherein said mapping step comprises the steps of: 
 generating a relation between the binding response level and the concentration level for said TK1 protein comprising immunoreactive material using recombinant TK1; and    determining said concentration level from said determined IM binding response level and said generated relation.    
     
     
         12 . The method according to  claim 1 , wherein said IM binding response determining step comprises the steps of: 
 contacting a TK1 protein affinity ligand with a body fluid sample from said subject, said ligand binds specifically to said TK1 protein; and    determining an amount of ligand binding in said sample.    
     
     
         13 . The method according to  claim 2 , further comprising the steps of: 
 contacting a TK1 protein affinity ligand with a body fluid sample from said subject, said ligand binds specifically to said TK1 protein; and    determining an amount of ligand binding in said sample, said decision support information being generated based on said amount of ligand binding.    
     
     
         14 . The method according to  claim 12 , wherein said ligand is an antibody that binds specifically to the C-terminal portion of TK1.  
     
     
         15 . The method according to  claim 12 , wherein said ligand is an antibody that is produced against a peptide sequence selected from: 
 amino acid sequence according to SEQ ID NO: 1; and    amino acid sequence according to SEQ ID NO: 2.    
     
     
         16 . The method according to  claim 12 , wherein said ligand binding determining step comprises the step of measuring said ligand binding by an enhanced chemoluminescence (ECL) dot blot immunoassay.  
     
     
         17 . The method according to  claim 1 , wherein said cancer disease is a solid tumor cancer disease.  
     
     
         18 . The method according to  claim 1 , wherein said likelihood of progress of said cancer disease is estimated based directly on said determined IM binding response level.  
     
     
         19 . The method according to  claim 1 , wherein said likelihood of progress of said cancer disease is estimated without determination of an enzyme activity level of TK1.  
     
     
         20 . The method according to  claim 2 , wherein said decision support is generated based directly on said determined IM binding response level.  
     
     
         21 . The method according to  claim 2 , wherein said decision support is generated based without determination of an enzyme activity level of TK1.  
     
     
         22 . A system for predicting progression of a cancer disease in a subject treated for said cancer disease, comprising means for estimating a likelihood of progress of said cancer disease based on a determined binding response level of an immunoreactive material (IM) comprising enzymatically active and inactive thymidine kinase 1 (TK1) protein.  
     
     
         23 . The system according to  claim 22 , wherein said TK1 protein comprising immunoreactive material comprises at least one of: 
 TK1 protein; and    a complex of TK1 protein and another molecule.    
     
     
         24 . The system according to  claim 22 , further comprising means for mapping said determined IM binding response level to a concentration level of said TK1 protein comprising immunoreactive material, and said estimating means is configured for estimating said likelihood progress of said cancer disease based on said determined concentration level.  
     
     
         25 . The system according to  claim 22 , wherein said estimating means is configured for estimating said likelihood of progress of said cancer disease based on a first IM binding response level determined in said subject no later than one month after initiation of said cancer treatment and on a second IM binding response level determined in said subject after initiation of said cancer treatment.  
     
     
         26 . The system according to  claim 22 , wherein said IM binding response level is determined based on measurement of ligand binding of a TK1 protein affinity ligand that binds specifically to the C terminal portion of TK1 protein in a sample from said subject.  
     
     
         27 . The system according to  claim 22 , wherein said IM binding response level is determined based on measurement of ligand binding of an antibody that is produced against a peptide sequence selected from: 
 amino acid sequence according to SEQ ID NO: 1; and    amino acid sequence according to SEQ ID NO: 2.    
     
     
         28 . The system according to  claim 22 , wherein said estimating means is adapted for estimating said likelihood of progress of said cancer disease based directly on said determined IM binding response level.  
     
     
         29 . The system according to  claim 22 , wherein said estimating means is adapted for estimating said likelihood of progress of said cancer disease without determination of an enzyme activity level of TK1.  
     
     
         30 . The method according to  claim 2 , wherein said TK1 protein comprising immunoreactive material is selected from at least one of: 
 TK1 protein; and    a complex of TK1 protein and another molecule.    
     
     
         31 . The method according to  claim 5 , wherein said first IM binding response level is determined in said subject before initiation of said cancer treatment.  
     
     
         32 . The method according to  claim 5 , wherein said second IM binding response level is determined in said subject within the first six months following initiation of said cancer treatment.  
     
     
         33 . The method according to  claim 10 , wherein said mapping step comprises the steps of: 
 generating a relation between the binding response level and the concentration level for said TK1 protein comprising immunoreactive material using recombinant TK1; and    determining said concentration level from said determined IM binding response level and said generated relation.    
     
     
         34 . The method according to  claim 13 , wherein said ligand is an antibody that binds specifically to the C-terminal portion of TK1.  
     
     
         35 . The method according to  claim 13 , wherein said ligand is an antibody that is produced against a peptide sequence selected from: 
 amino acid sequence according to SEQ ID NO: 1; and    amino acid sequence according to SEQ ID NO: 2.