Novel therapeutic targets in cancer

Abstract

The present invention relates to novel sequences for use in detection, diagnosis and treatment of cancers, especially lymphomas. The invention provides cancer-associated (CA) polynucleotide sequences whose expression is associated with cancer. The present invention provides CA polypeptides associated with cancer that are present on the cell surface and present novel therapeutic targets against cancer. The present invention further provides diagnostic compositions and methods for the detection of cancer. The present invention provides monoclonal and polyclonal antibodies specific for the CA polypeptides. The present invention also provides diagnostic tools and therapeutic compositions and methods for screening, prevention and treatment of cancer.

1 . A method of screening for anti-cancer compounds that modulate a biological activity of a TGFβ2 gene product, said method comprising contacting a candidate anti-cancer compound with a cell that expresses TGFβ2 and detecting a difference between the biological activity of TGFβ2 in the presence and absence of the candidate anti-cancer compound, wherein a difference between the level of biological activity of TGFβ2 in the presence and absence of the candidate anti-cancer compound indicates that the candidate anti-cancer agent has anti-cancer activity and wherein the cancer is prostate or breast cancer. 
     
     
         2 . The method of  claim 1 , wherein said biological activity is serine/threonine kinase signaling. 
     
     
         3 . The method of  claim 1  wherein said candidate anti-cancer compound is selected from the group consisting of a small molecule, an antibody, an antisense polynucleotide, and an RNAi molecule. 
     
     
         4 . A method for screening for anti-cancer compounds capable of modulating the activity of a CA protein (CAP), wherein said CAP is encoded by a nucleic acid comprising a nucleotide sequence at least 95% identical to SEQ ID NO:10 or SEQ ID NO:11, the method comprising contacting a cell that expresses the CAP with a candidate anti-cancer compound; and comparing the effect of the candidate anti-cancer compound on expression of the CAP in the presence of the candidate anti-cancer compound to expression of the CAP in the absence of the candidate anti-cancer compound;
 wherein a candidate anti-cancer compound which modulates the expression of the CAP is identified as an anti-cancer compound capable of modulating the activity of the CAP.   
     
     
         5 . The method of  claim 5  wherein the CAP is encoded by a nucleic acid comprising the nucleotide sequence of SEQ ID NO:10. 
     
     
         6 . The method of  claim 5  wherein the CAP is encoded by a nucleic acid comprising the nucleotide sequence of SEQ ID NO:11. 
     
     
         7 . The method of  claim 5  wherein the cancer is prostate or breast cancer. 
     
     
         8 . The method of  claim 5  wherein said candidate anti-cancer compound is selected from the group consisting of a small molecule, an antibody, an antisense polynucleotide, and an RNAi molecule. 
     
     
         9 . The method of  claim 1 , wherein said biological activity is serine/threonine kinase signaling. 
     
     
         10 . A method of screening for anti-cancer compounds comprising comparing the level of gene expression in a first biological sample in the presence of a candidate anti-cancer compound to the level of gene expression in a second biological sample in the absence of the candidate anti-cancer compound; wherein the gene comprises a nucleotide sequence at least 95% identical to a SEQ ID NO:10 or encodes a nucleic acid comprising a nucleotide sequence at least 95% identical to a SEQ ID NO:11, and wherein a candidate anti-cancer compound that decreases the level of gene expression in the first biological sample as compared to the second biological sample is identified as an anti-cancer compound. 
     
     
         11 . The method of  claim 10  wherein the cancer is prostate or breast cancer. 
     
     
         12 . The method of  claim 10  wherein the first biological sample is a test sample and the second biological sample comprises a normal control. 
     
     
         13 . The method of  claim 10  wherein gene expression is determined by measuring the level of a gene expression product. 
     
     
         14 . The method of  claim 13  wherein the gene expression product is mRNA or a polypeptide. 
     
     
         15 . The method of  claim 10  wherein the first biological sample comprises prostate or breast tissue. 
     
     
         16 . The method of  claim 10  wherein the candidate anti-cancer compound decreases the level of gene expression by at least 50% in the first biological sample as compared to the level of the gene expression in the second biological sample. 
     
     
         17 . The method of  claim 13  wherein the gene expression product is a nucleic acid comprising a nucleotide sequence of SEQ ID NO:11. 
     
     
         18 . The method of  claim 13  wherein the gene expression product is a polypeptide comprising an amino acid sequence of SEQ ID NO:12. 
     
     
         19 . The method of  claim 10  wherein said candidate anti-cancer compound is selected from the group consisting of a small molecule, an antibody, an antisense polynucleotide, and an RNAi molecule. 
     
     
         20 . A method of screening for anti-cancer compounds, comprising comparing the level of TGF-β2 activity in a first biological sample in the presence of a candidate anti-cancer compound to the level of TGF-β2 activity in a second biological sample in the absence of the candidate anti-cancer compound; wherein a candidate anti-cancer compound that decreases the level of TGF-β2 activity in the first biological sample as compared to the second biological sample is identified as an anti-cancer compound. 
     
     
         21 . The method of  claim 20  wherein the first biological sample is a test sample and the second biological sample comprises a normal control. 
     
     
         22 . The method of  claim 20  wherein the first biological sample comprises prostate or breast tissue. 
     
     
         23 . The method of  claim 20  wherein the cancer is prostate or breast cancer. 
     
     
         24 . The method of  claim 20  wherein said candidate anti-cancer compound is selected from the group consisting of a small molecule, an antibody, an antisense polynucleotide, and an RNAi molecule.