In vitro method for identifying compounds for cancer therapy

Abstract

The present invention relates to an in vitro method for identifying and evaluating compounds useful in the treatment of different types of cancer, especially lung, breast, colorectal and bladder cancer in an individual, for determining the stage or severity of said cancer in the individual, or for monitoring the effect of the therapy administered to an individual having said cancer; to finding, identifying, developing and evaluating the efficacy of compounds for the therapy of said cancer, for the purpose of developing new medicinal products; as well as to agents inhibiting the expression and/or activity of the choline kinase alpha protein and/or the effects of this expression.

1 . An in vitro method for identifying and evaluating the effectiveness of compounds for cancer therapy comprising:
 a) placing a culture of tumor cells in contact with the candidate compound, under the suitable conditions and for the suitable time to allow them to interact,   b) detecting and quantifying the expression levels of the choline kinase alpha gene or the choline kinase alpha protein, and   c) comparing said expression levels with those of the control cultures of tumor cells not treated with the candidate compound.   
     
     
         2 . The in vitro method according to  claim 1  wherein the cancer is selected from the group consisting of lung cancer, breast cancer, colorectal cancer or bladder cancer. 
     
     
         3 . An agent that inhibits the expression and/or activity of the choline kinase alpha protein, or ill that they inhibit the carcinogenic effects of choline kinase alpha protein overexpression. 
     
     
         4 . The agent according to  claim 3 , selected from the group formed by:
 a) an antibody, or combination of antibodies, specific against one or more epitopes present in the choline kinase alpha protein; a fragment of an antibody or an antibody chain,   b) cytotoxic agents inhibiting the carcinogenic effects of the overexpression and/or activity of the choline kinase alpha protein, and   c) antagonist compounds of the choline kinase alpha protein, inhibiting the carcinogenic effects of the expression and/or activity of the choline kinase alpha protein.   
     
     
         5 . A method for the treatment of cancer, comprising administering to a patient in need of such treatment a therapeutically effective amount of the agents according to  claim 3 . 
     
     
         6 . The method according to  claim 5  wherein the cancer is selected from the group consisting of lung cancer, breast cancer, colorectal cancer or bladder cancer. 
     
     
         7 . A pharmaceutical composition comprising a therapeutically effective amount of one or several agents according to  claim 3  together with at least one pharmaceutically acceptable excipient. 
     
     
         8 . The pharmaceutical composition according to  claim 7 , wherein it contains another active ingredient. 
     
     
         9 . The pharmaceutical composition according to  claim 8  wherein said another active ingredient is an agent which does not inhibit the function of the choline kinase alpha protein. 
     
     
         10 . (canceled) 
     
     
         11 . (canceled) 
     
     
         12 . (canceled) 
     
     
         13 . An in vitro method of monitoring the effect of a therapy administered to a cancer patient, the method comprising
 a) evaluating the choline kinase alpha protein expression level in a tissue sample extracted from the patient who is being administered an anti-tumor agent, preferably an agent, by means of the determination in said sample of at least one parameter related to the choline kinase alpha protein which is selected from the level of its messenger RNA, the concentration of said protein or its enzymatic activity, and   b) the comparison of the obtained value with the value corresponding to one or more normal non-cancerous tissue samples.   
     
     
         14 .- 16 . (canceled) 
     
     
         17 . The method according to  claim 13  wherein the anti-tumor agent is an agent that inhibits the expression and/or activity of the choline kinase alpha protein, or that inhibit the carcinogenic effects of choline kinase alpha protein overexpression. 
     
     
         18 . The method according to  claim 13  wherein the anti-tumor agent is pharmaceutical composition comprising a therapeutically effective amount of one or several agents that inhibit the expression and/or activity of the choline kinase alpha protein, or that inhibit the carcinogenic effects of choline kinase alpha protein overexpression, together with at least one pharmaceutically acceptable excipient. 
     
     
         19 . The agent according to  claim 4  wherein the antibody or combination of antibodies, specific against one or more epitopes present in the choline kinase alpha protein is a human or a humanized monoclonal antibody. 
     
     
         20 . The agent according to  claim 4  wherein the cytotoxic agents is selected from the group consisting of toxins, molecules with radioactive atoms, chemotherapeutic agents, peptides, phosphopeptides, anti-sense molecules, ribozymes, triple helix molecules, double strand RNA, and siRNA.