Tumor-specific P450 protein

Abstract

The discovery that CYP1B1 protein is detectable in a wide range of human cancers of different histogenetic types, but is not detectable in non-cancerous tissues, gives rise to diagnostic methods for detecting tumors based on this protein as a marker, and to the possibility of tumor therapies involving the protein. A diagnostic method may include the steps of (a) obtaining from a patient a tissue sample to be tested for the presence of cancer cells; (b) producing a prepared sample in a sample preparation process; (c) contacting the prepared sample with an antibody that reacts with human CYP1B1 protein; and (d) detecting binding of the antibody to CYP1B1 protein in the prepared sample.

What is claimed is:  
     
         1 . A composition comprising a compound that is selectively metabolized by CYP1B1 to generate a cytotoxic substance that kills or inhibits the growth of a tumor cell.  
     
     
         2 . The composition of  claim 1 , wherein the compound is non-toxic prior to its metabolism by CYP1B1.  
     
     
         3 . An anti-cancer drug comprising an amount of the composition of  claim 1  effective to kill or inhibit the growth of a tumor cell when administered to an individual having cancer.  
     
     
         4 . The anti-cancer drug of  claim 3 , wherein the tumor cell is a tumor cell of the bladder, brain, breast, colon, connective tissue, kidney, lung, lymph node, esophagus, ovary, skin, stomach, testis, or uterus.  
     
     
         5 . A composition comprising a compound that is selectively metabolized by CYP1B1 to generate a substance that renders a tumor cell susceptible to a cytotoxic agent.  
     
     
         6 . An anti-cancer drug comprising an amount of the composition of  claim 5  effective to render a tumor cell susceptible to a cytotoxic agent when administered to an individual having cancer.  
     
     
         7 . The anti-cancer drug of  claim 6 , wherein the tumor cell is a tumor cell of the bladder, brain, breast, colon, connective tissue, kidney, lung, lymph node, esophagus, ovary, skin, stomach, testis, or uterus.  
     
     
         8 . A method of killing or inhibiting the growth of a tumor cell, the method comprising contacting a tumor cell expressing CYP1B1 with the composition of  claim 1 , wherein the CYP1B1 expressed by the tumor cell metabolizes the compound to generate the cytotoxic substance and thereby kill or inhibit the growth of the tumor cell.  
     
     
         9 . The method of  claim 8 , wherein the tumor cell is a tumor cell of the bladder, brain, breast, colon, connective tissue, kidney, lung, lymph node, esophagus, ovary, skin, stomach, testis, or uterus.  
     
     
         10 . A method of rendering a tumor cell susceptible to a cytotoxic agent, the method comprising contacting a tumor cell expressing CYP1B1 with the composition of  claim 5 , wherein the CYP1B1 expressed by the tumor cell metabolizes the compound to generate the substance and thereby render the tumor cell susceptible to the cytotoxic agent.  
     
     
         11 . The method of  claim 10 , further comprising contacting the tumor cell with an amount of the cytotoxic agent effective to kill or inhibit the growth of the tumor cell.  
     
     
         12 . The method of  claim 11 , wherein the tumor cell is a tumor cell of the bladder, brain, breast, colon, connective tissue, kidney, lung, lymph node, esophagus, ovary, skin, stomach, testis, or uterus.  
     
     
         13 . A method of treating cancer, the method comprising administering to an individual diagnosed as having a tumor an amount of the composition of  claim 1  effective to kill or inhibit the growth of a tumor cell in the individual.  
     
     
         14 . The method of  claim 13 , further comprising detecting expression of CYP1B 1 in the tumor prior to the administration of the composition.  
     
     
         15 . The method of  claim 13 , wherein the administration of the composition does not result in liver toxicity in the individual.  
     
     
         16 . The method of  claim 13 , wherein the administration of the composition does not result in systemic toxicity in the individual.  
     
     
         17 . The method of  claim 13 , wherein the tumor is a tumor of the bladder, brain, breast, colon, connective tissue, kidney, lung, lymph node, esophagus, ovary, skin, stomach, testis, or uterus.  
     
     
         18 . A method of treating cancer, the method comprising: 
 administering to an individual diagnosed as having a tumor an amount of the composition of  claim 5  effective to render a tumor cell in the individual susceptible to the cytotoxic agent; and    administering to the individual an amount of the cytotoxic agent effective to kill or inhibit the growth of the tumor cell.    
     
     
         19 . The method of  claim 18 , further comprising detecting expression of CYP1B1 in the tumor prior to the administration of the composition.  
     
     
         20 . The method of  claim 18 , wherein the administration of the composition does not result in liver toxicity in the individual.  
     
     
         21 . The method of  claim 18 , wherein the administration of the composition does not result in systemic toxicity in the individual.  
     
     
         22 . The method of  claim 18 , wherein the tumor is a tumor of the bladder, brain, breast, colon, connective tissue, kidney, lung, lymph node, esophagus, ovary, skin, stomach, testis, or uterus.  
     
     
         23 . A method of preparing an anti-cancer compound, the method comprising: 
 selecting a compound that is metabolized by CYP1B1; and    preparing the compound as a non-toxic substance that is metabolized by CYP1B1 to generate a cytotoxic substance that kills or inhibits the growth of a tumor cell.    
     
     
         24 . The method of  claim 23 , wherein the compound is selected by screening to identify compositions that are metabolized by CYP1B 1.  
     
     
         25 . The method of  claim 23 , wherein the compound is selected by designing compositions that are metabolized by CYP1B1.  
     
     
         26 . A method of preparing an anti-cancer compound, the method comprising: 
 selecting a compound that is metabolized by CYP1B1; and    preparing the compound as a non-toxic substance that is metabolized by CYP1B1 to generate a moiety that renders a tumor cell susceptible to a cytotoxic agent.    
     
     
         27 . The method of  claim 26 , wherein the compound is selected by screening to identify compositions that are metabolized by CYP1B1.  
     
     
         28 . The method of  claim 26 , wherein the compound is selected by designing compositions that are metabolized by CYP1B1.