Cancer related isoforms of components of transcription factor complexes as biomarkers and drug targets

Abstract

The invention is related to isoforms of components of transcription factor complexes that are specifically expressed in cancer cells. These isoforms can be used as biomarkers for detection, diagnosis, prognosis and monitoring of treatments of cancer, and as drug targets of pharmaceutical compositions for the treatment of various cancers expressing the targeted isoforms. Methods, molecules, materials and kits for these uses are disclosed.

What is claimed is: 
     
         1 . An isolated, recombinant or synthetic isoform of a transcriptional co-regulator selected from the isoforms shown in SEQ ID NO: 4-207, or a peptide of at least 6 amino acids in length that specifically binds thereto, wherein:
 the isoform is an isoform of MED (SEQ ID NO: 4, 5, 87-93, 95-99, 105-164),   the isoform is an isoform of SWI/SNF (SEQ ID NO: 165-201),   the isoform is an isoform of GTF (SEQ ID NO: 6-11, 13-15, 17-56),   the isoform is an isoform of TAF (SEQ ID NO: 57-86), or   the isoform is an isoform of a co-activator or co-repressor (SEQ ID NO: 202-207)   
     
     
         2 . The peptide of  claim 1  that is at least 12 amino acids in length. 
     
     
         3 . The isoform of  claim 1 , which is a fusion protein comprising the isoform fused with a heterologous peptide. 
     
     
         4 . The fusion protein of  claim 3 , wherein the heterologous peptide is selected from the group consisting of SEQ ID NO: 1-3. 
     
     
         6 . An antibody that specifically binds an isoform of  claim 1 . 
     
     
         7 . The antibody of claim  5 , which is labeled with a detectable marker. 
     
     
         8 . A polynucleotide that encodes an isoform of  claim 1  or a complement thereof. 
     
     
         9 . The isoform of  claim 1 , and a pharmaceutically acceptable carrier. 
     
     
         10 . A method for detecting cancer in a tissue specimen comprising contacting the tissue specimen with assay reagents capable of detecting the presence of an isoform of  claim 1 , wherein presence of the isoform is indicative of cancer, and wherein the cancer is melanoma, colorectal cancer, lung cancer, hepatoma, pancreatic cancer, prostate cancer, gliomas, glioblastoma, neuroblastoma, sarcoma, chondrosarcoma, breast cancer, ovarian cancer, or teratocarcinoma. 
     
     
         11 . The method of  claim 10 , wherein the assay reagents comprise a detectable molecule that specifically binds an isoform of  claim 1  and the method further comprises detecting binding of the detectable molecule, wherein binding of the detectable molecule is indicative of cancer. 
     
     
         12 . The method of  claim 11 , wherein the molecule that specifically binds the isoform is an antibody. 
     
     
         13 . The method of  claim 12 , wherein the antibody is labeled with a detectable marker. 
     
     
         14 . A method for monitoring cancer in a subject, the method comprising:
 (a) assaying a tissue specimen obtained from the subject to measure the amount of an isoform of  claim 1  present in the specimen; and   (b) comparing the amount of the isoform present in the specimen to the amount of isoform determined under a previous condition, wherein a change in the amount of the isoform is indicative of a change in the progression of the cancer, and wherein the cancer is melanoma, colorectal cancer, lung cancer, hepatoma, pancreatic cancer, prostate cancer, gliomas, glioblastoma, neuroblastoma, sarcoma, chondrosarcoma, breast cancer, ovarian cancer, or teratocarcinoma.   
     
     
         15 . The method of  claim 14 , wherein the assaying comprises contacting the specimen with a detectable molecule that specifically binds an isoform of  claim 1 , wherein a change in the level of binding of the detectable molecule is indicative of a change in the progression of the cancer. 
     
     
         16 . The method of  claim 14 , wherein the assaying of step (a) comprises determining the percentage of cancer cells in the tissue specimen to which the isoform binds and/or determining the quantity of binding of the detectable molecule in the tissue specimen. 
     
     
         17 . The method of  claim 14 , wherein the molecule that specifically binds the isoform is an antibody. 
     
     
         18 . The method of  claim 17 , wherein the antibody is labeled with a detectable marker. 
     
     
         19 . A method of killing cancer cells, the method comprising contacting the cancer cells with the peptide of  claim 1 , wherein the cancer is melanoma, colorectal cancer, lung cancer, hepatoma, pancreatic cancer, prostate cancer, gliomas, glioblastoma, neuroblastoma, sarcoma, chondrosarcoma, breast cancer, ovarian cancer, or teratocarcinoma. 
     
     
         20 . A method of treating cancer in a subject, the method comprising administering to the subject an effective amount of the isoform of  claim 9 , wherein the cancer is melanoma, colorectal cancer, lung cancer, hepatoma, pancreatic cancer, prostate cancer, gliomas, glioblastoma, neuroblastoma, sarcoma, chondrosarcoma, breast cancer, ovarian cancer, or teratocarcinoma.