Novel compositions and methods for the identification, assessment, prevention, and therapy of human cancers

Abstract

The present invention is directed to the identification of markers that can be used to determine whether tumors are sensitive or resistant to a therapeutic agent. The present invention is also directed to the identification of therapeutic targets. The invention features a number of “sensitivity markers.” These are markers that are expressed in most or all cell lines that are sensitive to treatment with an agent and which are not expressed (or are expressed at a rather low level) in cells that are resistant to treatment with that agent. The invention also features a number of “resistance markers.” These are markers that are expressed in most or all cell lines that are resistant to treatment with an agent and which are not expressed (or are expressed at a rather low level) in cells that are sensitive to treatment with that agent.

1 . A method for determining whether paclitaxel can be used to reduce the growth of a tumor, comprising the steps of: 
 a) obtaining a sample of tumor cells;    b) determining whether the tumor cells express one or more markers identified in Tables 1, 2, 3 or 4, thereby determining whether paclitaxel can be used to reduce the growth of a tumor.    
     
     
         2 . The method of  claim 1 , wherein the level of expression is determined by detecting the amount of mRNA that is encoded by the one or more markers present in the sample.  
     
     
         3 . The method of  claim 1 , wherein the level of expression is determined by detecting the amount of protein that is encoded by said one or more markers present in the sample.  
     
     
         4 . The method of  claim 1 , wherein expression of one or more sensitivity markers identified in Tables 1 and 3 indicates that paclitaxel can be used.  
     
     
         5 . The method of  claim 1 , wherein expression of one or more resistance markers identified in Tables 2 and 4 indicates that paclitaxel cannot be used.  
     
     
         6 . A method for determining whether paclitaxel can be used to reduce the growth of a tumor, comprising the steps of: 
 a) obtaining a sample of tumor cells;    b) exposing the tumor cells to paclitaxel; and    c) determining the level of expression in the tumor cells of one or more markers identified in Tables 1, 2, 3, or 4 in the sample exposed to paclitaxel and in a sample of tumor cells that is not exposed to paclitaxel, thereby determining whether paclitaxel can be used to reduce the growth of a tumor.    
     
     
         7 . The method of  claim 6 , wherein the level of expression is determined by detecting the amount of mRNA that is encoded by the one or more markers present in the sample.  
     
     
         8 . The method of  claim 6 , wherein the level of expression is determined by detecting the amount of protein that is encoded by the one or more markers present in the sample.  
     
     
         9 . The method of  claim 6 , wherein increased expression in the presence of paclitaxel of one or more of the sensitivity markers identified in Tables 1 and 3 indicates that paclitaxel can be used to reduce the growth of the tumor.  
     
     
         10 . The method of  claim 6 , wherein increased expression in the presence of paclitaxel of one or more of the resistance markers identified in Tables 2 and 4 indicates that paclitaxel cannot be used to reduce the growth of the tumor.  
     
     
         11 . A method for determining whether treatment with paclitaxel should be continued in a cancer patient, comprising the steps of: 
 a) obtaining two or more samples comprising cancer cells from a patient during the course of treatment; and    b) determining the level of expression in the cancer cells of one or more markers identified in Tables 1, 2, 3, or 4 in the two or more samples, thereby determining whether treatment with paclitaxel should be continued in a cancer patient.    
     
     
         12 . The method of  claim 11 , wherein the level of expression is determined by detecting the amount of mRNA that is encoded by the one or more markers present in the sample.  
     
     
         13 . The method of  claim 11 , wherein the level of expression is determined by detecting the amount of protein that is encoded by the one or more markers present in the sample.  
     
     
         14 . The method of  claim 11 , wherein treatment with paclitaxel should be continued if the expression level of one or more of the sensitivity markers identified in Tables 1 and 3 does not decrease during the course of treatment.  
     
     
         15 . The method of  claim 11 , wherein treatment with paclitaxel should be discontinued if the expression level of one or more of the sensitivity markers identified in Tables 1 and 3 decreases during the course of treatment indicates that treatment.  
     
     
         16 . The method of  claim 11 , wherein treatment with paclitaxel should be continued if the expression level of one or more of the resistance markers identified in Tables 2 and 4 decreases during the course of treatment.  
     
     
         17 . An isolated nucleic acid molecule comprising a nucleotide sequence of SEQ ID NOs:1-88.  
     
     
         18 . A host cell which contains the nucleic acid molecule of  claim 17 .  
     
     
         19 . An isolated polypeptide which is encoded by a nucleic acid molecule comprising a nucleotide sequence of SEQ ID NOs:1-88.  
     
     
         20 . An antibody which selectively binds to a polypeptide of  claim 19 .  
     
     
         21 . A method for detecting the presence of a polypeptide of  claim 19  in a sample comprising: 
 a) contacting the sample with a compound which selectively binds to the polypeptide; and    b) determining whether the compound binds to the polypeptide in the sample, thereby detecting the presence of the polypeptide in the sample.    
     
     
         22 . A method for detecting the presence of a nucleic acid molecule of  claim 17  in a sample comprising: 
 a) contacting the sample with a nucleic acid probe or primer which selectively hybridizes to the nucleic acid molecule; and    b) determining whether the nucleic acid probe or primer binds to a nucleic acid molecule in the sample, thereby detecting the presence of the nucleic acid molecule in the sample.