Methods for diagnosing and treating prostate cancer
The invention is directed to a method of inhibiting prostate cancer cell proliferation using a substance that inhibits the activity of a 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 or protein expression in the subject.
1. A method of inhibiting proliferation of prostate cancer cells, which method 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,
(d) comparing the percentage of sAC protein positive nuclei in the sample to the percentage of sAC protein positive nuclei in a control sample, and
(e) administering a sAC inhibitor to the subject determined to have an increased percentage of sAC protein positive nuclei compared to the control sample, whereupon proliferation of the prostate cancer cells is inhibited.
2. The method of claim 1 , wherein the sAC inhibitor is a small molecule that inhibits sAC protein activity in the prostate cancer cell.
3. The method of claim 2 , wherein the small molecule is (E)-2-(1H-Benzo[d]imidazol-2-ylthio)-N′-(5-bromo-2-hydroxybenzylidene)propanehydrazide (KH7).
4. The method of claim 1 , wherein the sample of cells is obtained via biopsy, tissue excision, or fine needle aspiration (FNA).
5. 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.
6. The method of claim 1 , 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.