Methods of identifying and treating poor-prognosis cancers

Abstract

The present invention relates generally to methods for identifying cancer patients with a poor prognosis, and to therapeutic modalities for improving prognosis by combating metastasis and abrogating chemoresistance in cancer cells. Embodiments of the present invention provide an objective means of prognostication regarding the long-term outcome of an incident of cancer, breast cancer in particular. Therapeutic modalities include immunotherapy and anti-sense therapy. Prognosis is determined by measuring the number of copies of the metadherin gene in the patient's cells.

1 . A method of treating breast cancer comprising:
 a) providing;   i) a subject suspected of having breast cancer, and   ii) an agent that inhibits an activity of metadherin, and   b) administering said agent to said subject.   
     
     
         2 . The method of  claim 1 , wherein said breast cancer is a poor prognosis breast cancer. 
     
     
         3 . The method of  claim 2 , wherein said poor-prognosis breast cancer is a metastatic breast cancer. 
     
     
         4 . The method of  claim 2 , wherein said poor-prognosis breast cancer is a chemoresistant breast cancer. 
     
     
         5 . The method of  claim 2  wherein a cell from said poor prognosis breast cancer has more than 2 copies of a metadherin gene. 
     
     
         6 . The method of  claim 2  wherein a cell from said poor prognosis breast cancer has a metadherin gene copy number greater than a control cell. 
     
     
         7 . The method of  claim 6  wherein said control cell is selected from the group consisting of a non-cancerous cell from said subject, a non-cancerous cell from a reference subject, and a breast cancer cell from said reference subject. 
     
     
         8 . The method of  claim 1  wherein said agent is selected from the group consisting of an antibody to metadherin, a metadherin antisense molecule, and a small molecule. 
     
     
         9 . A method of making a prognosis in a subject with breast cancer comprising:
 a) providing a breast cancer cell from said subject,   b) determining, for said cell, a metadherin gene copy number, and   c) assigning a poor prognosis to said subject if said copy number is greater than 2   
     
     
         10 . A method of reducing the development of chemoresistant cancer cells in a subject treated with a chemotherapeutic agent, the method comprising:
 a) administering to said subject a pharmaceutically acceptable amount of said chemotherapeutic agent, and   b) administering to said subject an agent selected from the group consisting of an antibody to metadherin, a metadherin antisense molecule, and a small molecule.   
     
     
         11 . A method of determining variations in the copy-number of a gene across defined populations comprising the steps of:
 a) calculating an expression score based on expression differences between comparison groups for each of a plurality of genes having a genomic position on a chromosome,   b) ordering said expression scores based on said genomic position of each said gene,