Insulin-like growth factor system and cancer

Abstract

Method of monitoring or diagnosing disease conditions, including disease of the prostrate, that involve measuring a combination of tumour markers and at least one component of the IGF axis. The invention is exemplified with prostate cancer and benign prostatic hyperplasia, the tumor marker prostate specific antigen, and the insulin-like growth factors and their binding proteins.

We claim:  
     
         1 . A diagnostic tool for discriminating between benign and malignant disease, said tool comprising a indicator ratio selected from the group consisting of the concentration ratios: 
 a) IGF/kallikrein-like protein,    b) IGFBP/kallikrein-like protein,    c) IGF/IGFBP/kallikrein-like protein,    d) (intact IGFBP/total IGFBP)/kallikrein-like protein, and    e) (IGF+IGFBP)/kallikrein-like protein.    
     
     
         2 . The diagnostic tool of  claim 1 , said tool comprising a indicator ratio selected from the group consisting of: 
 IGF-I/free PSA,    b) intact IGFBP-3/free PSA,    c) (IGF-I/total IGFBP-3)/free PSA,    d) (intact IGFBP-3/total IGFBP-3)/free PSA,    e) (IGF-I+intact IGFBP-3)/free PSA, and    f) intact IGFBP3.    
     
     
         3 . The diagnostic tool of  claim 1 , wherein said tool is used to distinguish between benign conditions and lung cancer, breast cancer, colon cancer or prostate cancer.  
     
     
         4 . The diagnostic tool of  claim 1 , wherein said tool is used to distinguish between benign conditions and prostate cancer.  
     
     
         5 . A method of predicting cancer in a patient, comprising determining an indicator ratio selected from the group consisting of the concentration ratios of: 
 a) IGF/kallikrein-like protein,    b) IGFBP/kallikrein-like protein,    c) IGF/IGFBP/kallikrein-like protein,    d) (intact IGFBP/total IGFBP)/kallikrein-like protein, and    e) (IGF+IGFBP)/kallikrein-like protein, 
 whereby a indicator ratio different from a standard normal value indicates the existence of cancer.  
   
     
     
         6 . The method of  claim 5 , wherein the indicator ratio is selected from the group consisting of: 
 a) IGF-I/free PSA,    b) intact IGFBP-3/free PSA,    c) (IGF-I/total IGFBP-3)/free PSA,    d) (intact IGFBP-3/total IGFBP-3)/free PSA,    e) (IGF-I+intact IGFB-P-3)/free PSA, and    f) intact IGFBP3.    
     
     
         7 . The method of  claim 5 , wherein the indicator ration is used to distinguish between benign conditions and lung cancer, breast cancer, colon cancer or prostate cancer.  
     
     
         8 . The method of  claim 5 , wherein said indicator ratio is used to distinguish between benign conditions and prostate cancer.  
     
     
         9 . The method of  claim 8 , wherein the method further includes a measurement of free/total PSA.  
     
     
         10 . A method of monitoring cancer in a patient, comprising determining an indicator ratio selected from the group consisting of concentration ratios of: 
 a) IGF/kallikrein-like protein,    b) IGFBP/kallikrein-like protein,    c) IGF/IGFBP/kallikrein-like protein,    d) (intact IGFBP/total IGFBP)/kallikrein-like protein, and    e) (IGF+IGFBP)/kallikrein-like protein, 
 whereby a change in the indicator ratio indicates progression of the cancer.  
   
     
     
         11 . The method of  claim 10 , wherein the indicator ratio is selected from the group consisting of 
 a) IGF-I/free PSA,    b) intact IGFBP-3/free PSA,    c) (IGF-I/total IGFBP-3)/free PSA,    d) (intact IGFBP-3/total IGFBP-3)/free PSA,    e) (IGF-I+intact IGFBP-3)/free PSA, and    f) intact IGFBP3.    
     
     
         12 . The method of  claim 10  wherein the cancer is selected from the group consisting of lung cancer, colon cancer, breast cancer and prostate cancer.  
     
     
         13 . The method of  claim 11 , wherein the cancer is prostate cancer.  
     
     
         14 . The method of  claim 13 , wherein the method further includes a measurement of free/total PSA.  
     
     
         15 . A method of predicting cancer in a patient, comprising measuring at least two IGF axis components and a tumor marker.  
     
     
         16 . The method of  claim 15 , wherein the IGF axis components are selected fro the group consisting of IGF-I, IGF-II, IGFBP-1, IGFBP-2, IGFBP-3, IGFBP-4, IGFBP-5, IGFBP6, IGFBP-rP-1, IGFBP-rP-2, IGFBP-rP-3, IGFBP-rP4, IGFBP-rP-5, IGFBP-rP-6, IGFBP-rP-7, IGFBP-rP-8, IGFBP-rP-9, IGFBP protease, GH, GHBP, GH receptor, IGF receptor, IGF proteases, ALS, IGF receptor antagonists, and GH receptor antagonists and wherein the tumor marker is selected from the group consisting of PSA, kallikrein, S-100 protein, C219, GCDFP-15/gp17, riboflavin carrier protein, vitamin carrier proteins, human chorionic gonadotropin, alpha-fetoprotein, lactate dehydrogenase, cytokeratin 19 fragment, CYFRA 21-1, carbohydrate antigen 19.9, macrophage-colony stimulating factor, abnormal prothrombin PIVKA-II, tissue polypeptide antigen, carcinoembryonic antigen, cancer antigen 125, CA72-4, CA15-3, squamous cell antigen, neuron specific enolase, focal adhesion kinase, soluble CD44 (sCD44), soluble CD30 (sCD30), tissue polypeptide specific antigen (TPSA), total alkaline phosphatase (T-ALP), urinary Dpd/creatinine (Cre) ratios, bone specific alkaline phosphatase (B-ALP), N-acetylneuraminic (Neu5Ac), vascular endothelial growth factor (VEGF), glutathione peroxidase, melanoma antigen (MAGE), mesothelin and megakaryocyte potentiating factor (MPF), cyclin-dependent kinase inhibitor p27 (Kip1), PGP9.5, proliferating cell nuclear antigen (PCNA), Cyclin D1, epidermal Growth Factor (EGF), transforming growth factor alpha (TGF alpha), estrogen receptor-related protein (ERRP), multidrug resistance marker (MDRM), protein kinase C (PKC), Gs alpha, inhibin, cathepsin D, H19, the steroid hormones, p53, and cytokines and interleukins.