Cancer targets and uses thereof

Abstract

Methods and compositions are provided for assessing, treating, and preventing diseases, especially cancer, using cancer-associated targets (“CAT”). Methods and compositions are also provided for determining or predicting the effectiveness of a treatment for these diseases or for selecting a treatment, using CAT. Methods and compositions are further provided for modulating cell function using CAT. Also provided are compositions that modulate CAT (e.g., antagonists or agonists), such as antibodies, proteins, small molecule compounds, and nucleic acid agents (e.g., RNAi and antisense agents), as well as pharmaceutical compositions thereof. Further provided are methods of screening for agents that modulate CAT, and agents identified by these screening methods.

That which is claimed is: 
     
         1 . An isolated protein comprising an amino acid sequence selected from the group consisting of SEQ ID NOS:1-722, 1975, and 1977 and 1282-1974. 
     
     
         2 . A composition comprising the protein of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         3 . An isolated nucleic acid molecule comprising a nucleotide sequence selected from the group consisting of:
 a) SEQ ID NOS:723-1281, 1976, and 1978;   b) nucleotide sequences that encode a protein comprising an amino acid sequence selected from the group consisting of SEQ ID NOS:1-722, 1975, and 1977 and 1282-1974; and   c) nucleotide sequences that are completely complementary to the nucleotide sequences of a) or b).   
     
     
         4 . An isolated RNAi or antisense nucleic acid molecule that selectively binds to the nucleic acid molecule of  claim 3 . 
     
     
         5 . An isolated antibody that selectively binds to the protein of  claim 1 . 
     
     
         6 . The antibody of  claim 5 , wherein the antibody is at least one of a monoclonal, polyclonal, fully human, humanized, chimeric, single-chain, or anti-idiotypic antibody. 
     
     
         7 . A cell line, hybridoma, phage, or transgenic organism that produces the antibody of  claim 5 . 
     
     
         8 . The antibody of  claim 5 , wherein the antibody is coupled to a composition selected from the group consisting of detectable substances and therapeutic agents. 
     
     
         9 . A composition comprising the antibody of  claim 5  and a pharmaceutically acceptable carrier. 
     
     
         10 . An isolated antibody fragment of the antibody of  claim 5 , wherein the antibody fragment comprises a fragment selected from the group consisting of:
 a) an Fab fragment;   b) an F(ab′) 2  fragment; and   c) an Fv fragment.   
     
     
         11 . A method of modulating cell proliferation or apoptosis, the method comprising contacting a cell with the antibody of  claim 5 . 
     
     
         12 . The method of  claim 11 , wherein the method comprises either inhibiting proliferation of cancer cells or stimulating apoptosis of cancer cells. 
     
     
         13 . A method of modulating cell proliferation or apoptosis, the method comprising contacting a cell with the RNAi or antisense nucleic acid molecule of  claim 4 . 
     
     
         14 . A method of detecting the protein of  claim 1  in a sample, the method comprising contacting the sample with an isolated antibody that selectively binds to the protein and determining whether the antibody binds to the protein. 
     
     
         15 . A method of detecting the nucleic acid molecule of  claim 3  in a sample, the method comprising contacting the sample with an oligonucleotide that specifically hybridizes to the nucleic acid molecule and determining whether the oligonucleotide binds to the nucleic acid molecule. 
     
     
         16 . A method of diagnosing, prognosing, or determining risk of cancer in a subject, the method comprising detecting at least one molecule in a sample, wherein the presence or abundance of the molecule is indicative of cancer, and wherein the molecule is selected from the group consisting of:
 a) proteins comprising an amino acid sequence selected from the group consisting of SEQ ID NOS:1-722, 1975, and 1977 and 1282-1974;   b) antibodies that selectively bind to the protein of a);   c) nucleic acid molecules comprising a nucleotide sequence selected from the group consisting of SEQ ID NOS:723-1281, 1976, and 1978 and nucleotide sequences that encode the protein of a); and   d) nucleic acid molecules comprising a nucleotide sequence that is completely complementary to the nucleic acid molecule of c).   
     
     
         17 . A method of treating cancer, the method comprising administering a therapeutically effective amount of the antibody of  claim 5  to a subject. 
     
     
         18 . A method of screening agents, the method comprising contacting the protein of  claim 1  or a cell that expresses the protein with an agent, and assaying for whether the agent binds to the protein or modulates the function, activity, or expression of the protein. 
     
     
         19 . A composition comprising the agent identified by the method of  claim 18  and a pharmaceutically acceptable carrier. 
     
     
         20 . A method of determining or predicting the effectiveness of a treatment or selecting a treatment for administration to a subject having cancer, the method comprising detecting the presence, abundance, or activity of the protein of  claim 1  in a sample and determining or predicting the effectiveness of the treatment or selecting the treatment for administration based on the presence, abundance, or activity of the protein. 
     
     
         21 . A method of detecting or isolating a cancer stem cell, wherein the method comprises contacting the cancer stem cell with the antibody of  claim 5 . 
     
     
         22 . A method of detecting or isolating a protein expressed by a cancer stem cell, wherein the method comprises contacting the cancer stem cell with the antibody of  claim 5 . 
     
     
         23 . A method of selectively targeting a cancer stem cell, wherein the method comprises contacting a heterogenous population of cancer cells with the antibody of  claim 5 , wherein the antibody selectively binds to a cancer stem cell. 
     
     
         24 . The method of  claim 23 , wherein the method modulates proliferation or apoptosis of the cancer stem cell. 
     
     
         25 . The method of  claim 24 , wherein the method inhibits proliferation or stimulates apoptosis of the cancer stem cell.