Chemo-sensitivity assays using tumor cells exhibiting persistent phenotypic characteristics

Abstract

The assays, methods, tools and systems discussed herein represent an improved and unified system for monitoring the progression of an individual patient malignancy. The assays, methods, tools and systems discussed herein represent an improved and unified system for monitoring and for identifying cellular and secreted markers, for screening cells to detect phenotypic and genotypic drift and for predicting chemotherapeutic response of patient tumor cells to at least one therapeutic agent. The assays, methods, tools and systems discussed herein also represent an improved and unified system for monitoring and for screening multiple pharmaceutical agents for efficacy and long term effect as to a specific patient.

1 - 91 . (canceled) 
     
     
         92 . A method for predicting a cancer patient's response to a therapeutic agent, comprising the steps of:
 contacting tumor cells from a patient tumor sample with one or more therapeutic agents, and   measuring a response of the tumor cells to the one or more therapeutic agents, wherein said one or more therapeutic agents comprises Herceptin, an anti-EGFR antibody, or a small molecule kinase inhibitor, to thereby predict a cancer patient's response to the therapeutic agent.   
     
     
         93 . The method of  claim 92 , wherein the cancer is an epithelial carcinoma. 
     
     
         94 . The method of  claim 92 , wherein the cancer is breast cancer, colorectal cancer, ovarian cancer, or head and neck cancer. 
     
     
         95 . The method of  claim 92 , wherein the tumor cells are from one or more tumor explants. 
     
     
         96 . The method of  claim 95 , wherein the tumor cells are released from the one or more tumor explants, and expanded in monolayer culture. 
     
     
         97 . The method of  claim 96 , wherein a suspension of from 4,000 to 12,000 cells/mL is prepared, and inoculated into a plurality of segregated sites for testing. 
     
     
         98 . The method of  claim 92 , wherein the response of the tumor cells is measured with an apoptosis assay. 
     
     
         99 . The method of  claim 92 , wherein the response of the tumor cells is measured by determining the number of viable cells after treatment. 
     
     
         100 . The method of  claim 99 , wherein a dose-response curve is prepared. 
     
     
         101 . The method of  claim 92 , wherein the therapeutic agent is Herceptin. 
     
     
         102 . The method of  claim 92 , wherein the therapeutic agent is an anti-EGFR antibody. 
     
     
         103 . The method of  claim 102 , wherein the therapeutic agent is Erbitux. 
     
     
         104 . The method of  claim 92 , wherein the therapeutic agent is a small molecule kinase inhibitor. 
     
     
         105 . The method of  claim 104 , wherein the therapeutic agent is Tarceva or Iressa. 
     
     
         106 . The method of  claim 92 , further comprising, selecting the therapeutic agent(s) for treatment when the tumor cells are responsive to the agent(s). 
     
     
         107 . A method for predicting a cancer patient's response to a therapeutic agent, comprising the steps of:
 preparing a monolayer culture of tumor cells from a patient tumor sample,   contacting the tumor cells with one or more therapeutic agents, and   measuring viability of the tumor cells to the one or more therapeutic agents, wherein said one or more therapeutic agents comprises Herceptin, an anti-EGFR antibody or a small molecule kinase inhibitor, to thereby predict a cancer patient's response to the therapeutic agent.   
     
     
         108 . A method for predicting a cancer patient's response to a therapeutic agent, comprising the steps of:
 contacting tumor cells from a patient tumor sample with one or more therapeutic agents, and   measuring a response of the tumor cells to the one or more therapeutic agents, wherein said one or more therapeutic agents comprises pemetrexed, to thereby predict a cancer patient's response to the therapeutic agent.   
     
     
         109 . The method of  claim 108 , wherein the cancer is an epithelial carcinoma or mesothelioma 
     
     
         110 . The method of  claim 108 , wherein the tumor cells are from one or more tumor explants. 
     
     
         111 . The method of  claim 110 , wherein the tumor cells are released from the one or more tumor explants, and expanded in monolayer culture. 
     
     
         112 . The method of  claim 108 , wherein a suspension of from 4,000 to 12,000 cells/mL is prepared, and inoculated into a plurality of segregated sites for testing. 
     
     
         113 . The method of  claim 108 , wherein the response of the tumor cells is measured with an apoptosis assay. 
     
     
         114 . The method of  claim 108 , wherein the response of the tumor cells is measured by determining the number of viable cells after treatment. 
     
     
         115 . The method of  claim 108 , wherein a dose-response curve is prepared. 
     
     
         116 . The method of  claim 108 , further comprising, selecting the therapeutic agent for treatment when the tumor cells are responsive to the agent.