Gene amplification of coactivator coaa and uses thereof

Abstract

It has been discovered that amplifications in the gene coactivator activator (CoAA) blocks stem cell differentiation and induces cancer stem cells. One embodiment provides compositions and methods for treating or alleviating one or more symptoms associated with cancer due to gene amplifications in CoAA. Another embodiment provides methods and compositions for detecting cancer due to gene amplifications in CoAA. Still another embodiment provides methods for identifying compounds, antibodies and nucleic acid molecules that are useful for treating cancer due to gene amplifications in CoAA. Preferably the disclosed compositions antagonize or interfere with the CoAA amplicons and the biological activity of CoAA and or splice variants thereof.

1 . A method for detecting or assisting in the diagnosis of cancer comprising:
 detecting the presence of one or more coactivator activator amplicons in a biological sample obtained from a subject, wherein the presence of one or more amplicons in the biological sample is indicative of cancer.   
     
     
         2 . The method of  claim 1 , wherein detecting the presence of one or more amplicons is done by performing fluorescent in situ hybridization. 
     
     
         3 . The method of  claim 1 , wherein detecting the presence of one or more amplicons is done by performing quantitative polymerase chain reaction. 
     
     
         4 . The method of  claim 1 , wherein the biological sample is selected from the group consisting of blood, tissue, and cells. 
     
     
         5 . A method for treating cancer comprising:
 administering to a subject an effective amount of an antibody that binds specifically to CoAA, CoAA alternative splicing variants, or a combination thereof to alleviate one or more symptoms associated with cancer.   
     
     
         6 . The method of  claim 5 , wherein the antibody is selected from the group consisting of monoclonal, polyclonal, single chain, humanized, and chimeric. 
     
     
         7 . The method of  claim 5 , wherein the antibody comprises a protein transduction domain. 
     
     
         8 . A method for treating cancer comprising administering to a subject an effective amount of an inhibitory nucleic acid that hybridizes to a nucleic acid encoding CoAA or its alternative splicing variants including CoAM and inhibits expression of the nucleic acid. 
     
     
         9 . The method of  claim 8 , wherein the inhibitory nucleic acid is selected from the group consisting of siRNA, microRNA, and peptide nucleic acid. 
     
     
         10 . A method for treating cancer comprising administering to a subject an effective amount of an inhibitory nucleic acid that hybridizes to a nucleic acid within the CoAA amplicons to alleviate one or more symptoms associated with a cancer due to an amplification of CoAA. 
     
     
         11 . The method of  claim 10 , wherein the inhibitory nucleic acid is selected from the group consisting of aptamers, antisense DNA, and peptide nucleic acid. 
     
     
         12 . The method of  claim 10 , wherein the inhibitory nucleic acid comprises a cell penetrating peptide linked to the inhibitory nucleic acid. 
     
     
         13 . A method for treating cancer cells containing an amplification of the CoAA gene comprising
 administering the inhibitory nucleic acid of  claim 10  to a subject in need thereof.   
     
     
         14 . The method of  claim 13 , wherein the subject is human. 
     
     
         15 . A method of screening for compounds for treating cancer comprising:
 treating one or more cells comprising one or more CoAA amplicons with a test compound;   determining the expression levels of CoAA and its alternative splicing variants including CoAM in one or more cells treated with the test compound; and   selecting the test compound that inhibits the expression of CoAA or its alternative splicing variants including CoAM below predetermined baseline levels.