Assay to identify anti-cancer agents

Abstract

An in vitro method for identifying an anti-cancer agent, the therapeutic efficacy of which is enhanced upon administration with a second agent that increases the expression of OPRK1 and/or BAD, comprising the steps of:(a) co-incubating a population of cells with a target anti-cancer agent and said second agent and(b) measuring the cytotoxicity and/or cytostasis in the population of cells;wherein the therapeutic efficacy of the target anti-cancer agent is enhanced if the cytotoxicity and/or cytostasis of the target anti-cancer agent is increased compared to a control.

1 . An in vitro method for identifying an anti-cancer agent, the therapeutic efficacy of which is enhanced upon administration with a second agent that increases the expression of opioid receptor kappa-1 OPRK1, comprising the steps of:
 a) co-incubating a population of cells with a target anti-cancer agent and said second agent and   b) measuring the cytotoxicity and/or cytostasis in the population of cells;   wherein the second agent is selected from the group consisting of 6-β-naltrexol, naltrexone, methlynaltrexone or a pharmaceutically acceptable salt thereof, wherein the therapeutic efficacy of the target anti-cancer agent is identified as enhanced if the cytotoxicity and/or cytostasis of the target anti-cancer agent is increased compared to a control.   
     
     
         2 . The method of  claim 1 , further comprising the steps of:
 c) determining whether there is increased cytotoxicity and/or cytostasis compared to a control.   
     
     
         3 . The method according to  claim 1  or  2 , wherein the second agent is provided in an amount sufficient to increase the concentration of OPRK1 above the normal basal levels expected in the specific cancer cell type. 
     
     
         4 . The method according to  claim 1  or  2 , wherein the second agent is incubated with the population of cells prior to the addition of the target anti-cancer agent. 
     
     
         5 . The method according to  claim 4 , wherein the population of cells are incubated with the second agent for a sufficient time to enable the level of expression of OPRK1 to increase by at least 25% prior to addition of the target anti-cancer agent. 
     
     
         6 . The method according to  claim 1  or  2 , wherein the target anti-cancer agent and the second agent are administered to the population of cells simultaneously. 
     
     
         7 . The method according to  claim 1 , wherein the second agent is 6-β-naltrexol or a pharmaceutically acceptable salt thereof. 
     
     
         8 . The method according to  claim 7 , wherein the second agent is added to a final concentration of at least 0.34 ng/ml. 
     
     
         9 . The method according to  claim 8 , wherein the second agent is added to a final concentration of from 0.34 ng/ml to 3,400 ng/ml. 
     
     
         10 . The method according to  claim 9 , wherein the second agent is added to a final concentration of from 34 ng/ml to 3,400 ng/ml. 
     
     
         11 . The method according to  claim 10 , wherein the second agent is added to a final concentration of from 340 ng/ml to 3,400 ng/ml. 
     
     
         12 . The method according to  claim 1 , wherein the population of cells are, or are derived from, an immortalized cell line, preferably of human origin. 
     
     
         13 . The method according to  claim 1 , wherein the population of cells are, or are derived from, a tumour biopsy obtained from a subject having cancer. 
     
     
         14 . The method according to  claim 1 , wherein the method further comprises measuring the expression of OPRK1 in the population of cells before and/or after administration of the second agent.