Transcriptional biomarkers and methods for detecting and isolating cancer cells in body fluids and tissue specimens

Abstract

The invention provides molecules that target cancer-specific transcription complexes (CSTC), compositions and kits comprising CSTC-targeting molecules, and methods of using CSTC-targeting molecules for the treatment, detection and monitoring of cancer.

1 . An isolated peptide of fewer than 100 amino acids that specifically binds to:
 (a) SEQ ID NO: 11 and not SEQ ID NO: 10, or   (b) SEQ ID NO: 13 and not SEQ ID NO: 12.   
     
     
         2 . The peptide of  claim 1  that is labeled with a detectable marker. 
     
     
         3 . The peptide of  claim 1  that comprises the amino acid sequence of SEQ ID NO: 1 or a conservatively modified variant thereof having the amino acid sequence of SEQ ID NO: 7. 
     
     
         4 . The peptide of  claim 1  that comprises the amino acid sequence of SEQ ID NO: 2 or a conservatively modified variant thereof having the amino acid sequence of SEQ ID NO: 8. 
     
     
         5 . The peptide of  claim 1 , further comprising a cell penetrating peptide (CPP). 
     
     
         6 . The peptide of  claim 5 , wherein the CPP has the amino acid sequence RRRRRRR (SEQ ID NO: 3). 
     
     
         7 . The peptide of  claim 1 , further comprising a nuclear localizing signal (NLS). 
     
     
         8 . The peptide of  claim 7 , wherein the NLS has the amino acid sequence PKKRKV (SEQ ID NO: 4). 
     
     
         9 . The peptide of  claim 1 , wherein the peptide has the amino acid sequence PKKRKVRRRRRRRPQMQQNVFQYPGAGMVPQGEANF (TRAP100 P05; SEQ ID NO: 5) or PKKRKVRRRRRRRNDRLSDGDSKYSQTSHKLVQLL (BAF57 P12; SEQ ID NO: 6). 
     
     
         10 . The peptide of  claim 1 , wherein the peptide is a recombinant or synthetic peptide having the amino acid sequence PKKRKVRRRRRRRPQMQQNVFQYPGAGMVPQGEANF (TRAP100 P05; SEQ ID NO: 5), and wherein the peptide is labeled with a detectable marker. 
     
     
         11 . The peptide of  claim 1 , wherein the peptide is a recombinant or synthetic peptide having the amino acid sequence PKKRKVRRRRRRRNDRLSDGDSKYSQTSHKLVQLL (BAF57 P12; SEQ ID NO: 6), and wherein the peptide is labeled with a detectable marker. 
     
     
         12 . A method for detecting cancer in a tissue specimen, comprising:
 (a) contacting a tissue specimen with the peptide of  claim 1 , wherein the peptide has been labeled with a detectable marker to form a detectable molecule, and   (b) detecting presence of the detectable molecule, wherein presence of the detectable molecule is indicative of cancer.   
     
     
         13 . The method of  claim 12 , wherein the cancer is melanoma, glioblastoma, breast or colorectal cancer. 
     
     
         14 . The method of  claim 12 , wherein the tissue specimen is a tumor sample or cerebrospinal fluid. 
     
     
         15 . The method of  claim 12 , wherein the detectable marker comprises a fluorescent label. 
     
     
         16 . A kit comprising the peptide of  claim 2  and a container that is compartmentalized to receive the peptide. 
     
     
         17 . The kit of  claim 16 , further comprising an antibody that specifically recognizes and binds the peptide. 
     
     
         18 . The kit of  claim 17 , wherein the antibody is labeled with a detectable marker. 
     
     
         19 . The kit of  claim 16 , further comprising a label provided on the container, wherein the label indicates that the kit is for use in the detection of cancer. 
     
     
         20 . The kit of  claim 16 , wherein the peptide has the amino acid sequence PKKRKVRRRRRRRPQMQQNVFQYPGAGMVPQGEANF (TRAP100 P05; SEQ ID NO: 5) or PKKRKVRRRRRRRNDRLSDGDSKYSQTSHKLVQLL (BAF57 P12; SEQ ID NO: 6).