Methods and compositions for the identification and assessment of prostate cancer therapies and the diagnosis of prostate cancer

Abstract

The invention concerns two classes of differentially regulated genes: 1) genes that are more highly expressed in prostate cancer cells treated with testosterone than in untreated prostate cancer cells; and 2) genes that are more highly expressed in prostate cancer cells treated with bicalutamide, an anti-androgenic compound, than in untreated prostate cancer cells. Disclosed are methods for selecting and monitoring the effectiveness of therapeutic agents used for the treatment of prostate cancer. Also disclosed are methods for identifying novel therapeutic agents for the treatment of prostate cancer and methods and compositions for preventing, treating, and diagnosing prostate cancer.

1 . A method for determining whether a compound can be used to treat prostate cancer in a patient, comprising: 
 a) obtaining a patient biological sample;    b) determining the normalized expression level of one or more genes selected from the group consisting of SEQ ID NOS:1-40, 86-130 in the patient sample; c)    comparing the normalized expression level of the selected one or more genes determined in step b) with the normalized expression level of the selected one or more genes in a non-prostate cancer biological sample; and    d) identifying that a compound can be used to treat prostate cancer in the patient when the normalized expression level of the selected one or more genes in the patient sample is greater than the normalized expression level of the selected one or more genes in the non-prostate cancer biological sample.    
     
     
         2 . (canceled)  
     
     
         3 . A method for determining whether a treatment should be continued in a prostate cancer patient, comprising: 
 a) obtaining a patient biological sample;    b) determining the normalized expression level of one or more genes selected from the group consisting of SEQ ID NOS:1-40, 86-130 in the patient sample; c)    comparing the normalized expression level of the selected one or more genes determined in step b) with the normalized expression level of the selected one or more genes in a non-prostate cancer biological sample; and    d) discontinuing treatment when the normalized expression level of the selected one or more genes in the patient sample is greater than the normalized expression level of the selected one or more genes in the non-prostate cancer sample.    
     
     
         4 - 6 . (canceled)  
     
     
         7 . The method of  claim 1  wherein the normalized expression level of the selected one or more genes is determined by measuring the mRNA encoded by each of the selected one or more genes.  
     
     
         8 . The method of  claim 1  wherein the normalized expression level of the selected one or more genes is determined by measuring the amount of protein encoded by each of the selected one or more genes.  
     
     
         9 . The method of  claim 1  wherein the normalized expression level of the selected one or more genes is determined by measuring the activity of the protein encoded by each of the selected one or more genes.  
     
     
         10 . The method of  claim 1  wherein the selected genes are five or more genes selected from the group consisting of SEQ ID NOS:1-40, 86-130.  
     
     
         11 . The method of  claim 1  wherein the selected genes are ten or more genes selected from the group consisting of SEQ ID NOS:1-40, 86-130.  
     
     
         12 . The method of  claim 1  wherein the compound is an anti-androgenic compound.  
     
     
         13 . (canceled)  
     
     
         14 . The method of  claim 1  wherein the patient biological sample is derived from patient prostate cells, serum, interstitial fluid, blood, or seminal fluid.  
     
     
         15 - 18 . (canceled)  
     
     
         19 . A method for determining whether a compound can be used to treat prostate cancer, comprising: 
 a) measuring the expression level of one or more genes selected from the group consisting of SEQ ID NOS:41-85, 131-191 in a prostate cancer cell sample in the presence and absence of the compound; and    b) identifying the compound as useful for treating prostate cancer when the expression level of the selected one or more genes in the presence of the compound is greater than the expression level of the selected one or more genes in the absence of the compound.    
     
     
         20 . A method for determining whether a compound can be used to treat prostate cancer, comprising: 
 a) measuring the expression level of one or more genes selected from the group consisting of SEQ ID NOS:1-40, 86-130 in prostate cancer cell sample in the presence and absence of the compound; and    b) identifying the compound as useful for treating prostate cancer when the expression level of the selected one or more genes in the presence of the compound is less than the expression level of the selected one or more genes in the absence of the compound.    
     
     
         21 . The method of  claim 19  wherein the expression level of the selected one or more genes is determined by measuring the mRNA encoded by each of the selected one or more genes; measuring the amount of protein encoded by each of the selected one or more genes, or by measuring the activity of the protein encoded by each of the selected one or more genes.  
     
     
         22 - 23 . (canceled)  
     
     
         24 . The method of  claim 19  wherein the selected genes are five or more genes selected from the group consisting of SEQ ID NOS:41-85, 131-191.  
     
     
         25 . The method of  claim 19  wherein the selected genes are ten or more genes selected from the group consisting of SEQ ID NOS:41-85, 131-191.  
     
     
         26 - 27 . (canceled)  
     
     
         28 . A method for determining whether a treatment should be continued in a prostate cancer patient, comprising: 
 a) obtaining a patient biological sample;    b) determining the normalized expression level of one or more genes selected from the group consisting of SEQ ID NOS:41-85, 131-191 in the patient sample;    c) comparing the normalized expression level of the selected one or more genes determined in step b) with the normalized expression level of the selected one or more genes in a non-prostate cancer biological sample; and    d) discontinuing treatment when the normalized expression level of the selected one or more genes in the patient sample is less than or equal to the normalized expression level of the selected one or more genes in the non-prostate cancer sample.    
     
     
         29 . (canceled)  
     
     
         30 . The method of  claim 28  wherein the treatment is an anti-androgenic treatment.  
     
     
         31 . The method of  claim 28  wherein the patient biological sample is derived from patient prostate cells, serum, interstitial fluid, blood, or seminal fluid.  
     
     
         32 - 37 . (canceled)  
     
     
         38 . A method for determining whether an individual has or at risk for developing prostate cancer, comprising: 
 a) obtaining a biological sample from the individual;    b) determining the normalized expression level of one or more genes selected from the group consisting of SEQ ID NOS:1-40, 86-130 in the individual sample;    c) comparing the normalized expression level of the selected one or more genes determined in step b) with the normalized expression level of the selected one or more genes in a non-prostate cancer biological sample; and    d) indentifying the individual as having or being at risk for developing prostate cancer when the normalized expression level of the selected one or more genes in the individual sample is greater than the normalized expression level of the selected one or more genes in the non-prostate cancer sample.