Diagnosing and treating hormone resistant cancers

Abstract

Provided herein are methods and compositions related to diagnosing and treating hormone resistant cancers.

1 . A method of determining whether a cancer cell is sensitive to endocrine therapy comprising:
 a) obtaining a population of cancer cells; and   b) determining the level of expression or activity of Deleted in Breast Cancer-1 (DBC-1) in the cells, an increase in expression or activity of DBC-1 as compared to a control indicating that the cancer cells are not sensitive to endocrine therapy.   
     
     
         2 . The method of  claim 1 , wherein the cancer cells are endometrial cancer cells, breast cancer cells, ovarian cancer cells or prostate cancer cells. 
     
     
         3 . The method of  claim 1 , wherein step b) is carried out by determining the level of DBC-1 mRNA. 
     
     
         4 . The method of  claim 1 , wherein step b) is carried out by determining the level of DBC-1 protein. 
     
     
         5 . The method of  claim 4 , wherein step b) is carried out using a polyclonal antibody that binds DBC-1 in the region of amino acids 475-923. 
     
     
         6 .- 8 . (canceled) 
     
     
         9 . A method of determining whether a subject with cancer is suitable for treatment with endocrine therapy comprising:
 a) obtaining a biological sample comprising cancer cells from the subject; and   b) determining the level of expression or activity of DBC-1, an increase in expression or activity of DBC-1 as compared to a control indicating that the subject is not suitable for treatment with endocrine therapy.   
     
     
         10 . The method of  claim 9 , wherein the cancer cells are endometrial cancer cells, breast cancer cells, ovarian cancer cells or prostate cancer cells. 
     
     
         11 . The method of  claim 9 , wherein step b) is carried out by determining the level of DBC-1 mRNA. 
     
     
         12 . The method of  claim 9 , wherein step b) is carried out by determining the level of DBC-1 protein. 
     
     
         13 . The method of  claim 12 , wherein step b) is carried out using a polyclonal antibody that binds DBC-1 in the region of amino acids 475-923. 
     
     
         14 .- 16 . (canceled) 
     
     
         17 . A method of determining a susceptibility to hormone resistant cancer in a subject comprising:
 a) obtaining a biological sample comprising cancer cells from the subject; and   b) determining the level of expression or activity of DBC-1, wherein an increase in expression or activity of DBC-1 as compared to a control indicates that the subject is susceptible to hormone resistant cancer.   
     
     
         18 . The method of  claim 17 , wherein the subject has endometrial cancer, breast cancer, ovarian cancer or prostate cancer. 
     
     
         19 . The method of  claim 17 , wherein step b) is carried out by determining the level of DBC-1 mRNA. 
     
     
         20 . The method of  claim 17 , wherein step b) is carried out by determining the level of DBC-1 protein. 
     
     
         21 . The method of  claim 20 , wherein step b) is carried out using a polyclonal antibody that binds DBC-1 in the region of amino acids 475-923. 
     
     
         22 .- 24 . (canceled) 
     
     
         25 . A method of inducing apoptosis of cancer cells comprising:
 a) selecting a population of hormone resistant cancer cells, wherein the hormone resistant cancer cells express ER-α; and   b) contacting the hormone resistant cancer cells with an agent that inhibits expression of DBC-1.   
     
     
         26 . The method of  claim 25 , wherein the agent is an inhibitory nucleic acid. 
     
     
         27 . The method of  claim 26 , wherein the inhibitory nucleic acid is an siRNA. 
     
     
         28 .- 29 . (canceled) 
     
     
         30 . The method of  claim 25 , wherein the cancer cells are breast cancer cells, ovarian cancer cells or prostate cancer cells. 
     
     
         31 . A method of treating hormone resistant cancer in a subject, comprising:
 a) selecting a subject with hormone resistant cancer, wherein the cells of the hormone resistant cancer express ER-α; and   b) administering to the subject an agent that inhibits expression of DBC-1.   
     
     
         32 . The method of  claim 31 , wherein the agent is administered in an effective amount to induce apoptosis of the hormone resistant cancer cells. 
     
     
         33 . The method of  claim 31 , wherein the subject has endometrial cancer, breast cancer, ovarian cancer or prostate cancer. 
     
     
         34 . The method of  claim 31 , wherein the agent is comprised within a composition comprising the agent and a pharmaceutically acceptable carrier. 
     
     
         35 . The method of  claim 31 , wherein the agent is an inhibitory nucleic acid. 
     
     
         36 . The method of  claim 35 , wherein the inhibitory nucleic acid is an siRNA. 
     
     
         37 .- 38 . (canceled) 
     
     
         39 . The method of  claim 31 , further comprising administering a chemotherapeutic agent to the subject. 
     
     
         40 . The method of  claim 31 , further comprising administering radiation to the subject.