Methods for diagnosing and treating prostate cancer

Abstract

The invention is directed to a method of inhibiting prostate cancer cell proliferation using a substance that inhibits the activity of soluble adenylyl cyclase (sAC) protein. The invention also is directed to methods of diagnosing and prognosticating prostate cancer in a subject by evaluating sAC gene expression or sAC protein production in the subject.

1 . A method of inhibiting proliferation of prostate cancer cells, which method comprises contacting prostate cancer cells with a substance that inhibits that activity of soluble adenylyl cyclase (sAC) protein selected from a small interfering RNA (siRNA) and a short hairpin RNA (shRNA), whereupon proliferation of the prostate cancer cells is inhibited. 
     
     
         2 .- 3 . (canceled) 
     
     
         4 . The method of  claim 1 , wherein the substance that inhibits the activity of the sAC protein is an siRNA that specifically targets a gene encoding the sAC protein. 
     
     
         5 . The method of  claim 1 , wherein the substance that inhibits the activity of the sAC protein is administered to a male prostate cancer subject. 
     
     
         6 . A method for diagnosing prostate cancer in a male subject, which method comprises:
 (a) obtaining a sample of cells from the prostate of a male subject,   (b) assaying the sample for expression of the sAC gene or production of the sAC protein, and   (c) comparing the level of the sAC gene expression or the sAC protein production in the sample to a control, wherein overexpression of the sAC gene or overproduction of the sAC protein in the sample as compared to the control is indicative of prostate cancer in the male subject.   
     
     
         7 . A method for selecting a treatment option for a prostate cancer subject, which method comprises:
 (a) obtaining a sample of prostate cancer cells from a prostate cancer subject,   (b) assaying the sample for expression of the sAC gene or production of the sAC protein,   (c) comparing the level of the sAC gene expression or the sAC protein production in the sample to a control,   (d) prognosticating the prostate cancer in the subject based on the comparison performed in (c),   (e) selecting a treatment option for the subject based on the subject's prognosis in (d), and   (f) providing the treatment option to the subject.   
     
     
         8 . The method of  claim 6 , wherein the sample of cells is obtained via biopsy, tissue excision, or fine needle aspiration (FNA). 
     
     
         9 . The method of  claim 6 , wherein the sample is assayed for sAC gene expression. 
     
     
         10 . The method of  claim 6 , wherein the sample is assayed for sAC protein production. 
     
     
         11 . The method of  claim 7 , wherein prognosticating the prostate cancer in the subject comprises calculating a Gleason score and/or determining the prostate cancer stage for the sample. 
     
     
         12 . The method of  claim 7 , wherein the treatment option is active surveillance, surgery, radiation therapy, hormone therapy, chemotherapy, biologic therapy, bisphosphonate therapy, monoclonal antibody therapy, cryosurgery, high-intensity focused ultrasound, proton beam radiation therapy, or any combination of the foregoing treatment options. 
     
     
         13 . The method of  claim 7 , wherein the sample of cells is obtained via biopsy, tissue excision, or fine needle aspiration (FNA). 
     
     
         14 . The method of  claim 7 , wherein the sample is assayed for sAC gene expression. 
     
     
         15 . The method of  claim 7 , wherein the sample is assayed for sAC protein production. 
     
     
         16 . The method of  claim 5 , wherein the prostate cancer cells in the male cancer subject are characterized by overexpression of the sAC gene or overproduction of the sAC protein. 
     
     
         17 . The method of  claim 1 , wherein the method further comprises treatment of the subject with surgery, radiation therapy, hormone therapy, chemotherapy, biologic therapy, bisphosphonate therapy, monoclonal antibody therapy, cryosurgery, high-intensity focused ultrasound, proton beam radiation therapy, or any combination of the foregoing treatment options. 
     
     
         18 . The method of  claim 1 , which further comprises:
 (a) obtaining a sample of cells from the prostate of a male subject,   (b) assaying the sample for nuclear expression of the soluble adenylyl cyclase (sAC) protein,   (c) determining the percentage of sAC protein positive nuclei in the sample, and   (d) comparing the percentage of sAC protein positive nuclei in the sample to the percentage of sAC protein positive nuclei in a control sample,   wherein the substance that inhibits the activity of the sAC protein is administered to a male prostate cancer subject determined to have an increased percentage of sAC protein positive nuclei compared to the control sample.   
     
     
         19 . The method of  claim 18 , wherein nuclear expression of the sAC protein is determined with an anti-sAC antibody that binds to an epitope comprising the amino acid sequence of SEQ ID NO: 9.