Methods for assessing efficacy of chemotherapeutic agents

Abstract

Methods are provided for accurately predicting efficacy of chemotherapeutic agents. Methods of the invention increase the positive predictive value of chemosensitivity assays by assessing both the ability of a chemotherapeutic to destroy cells and the genetic propensity of those cells for resistance. Results obtained using methods of the invention provide insight into the in vivo effectiveness of a therapeutic, and lead to more effective chemotherapeutic treatment.

What is claimed is:  
     
         1 . A method for assessing efficacy of a chemotherapeutic agent, the method comprising: 
 conducting an assay to determine whether a chemotherapeutic agent affects cellular phenotype of a sample of tumor cells obtained from a patient;    determining whether said patient comprises a genetic characteristic associated with resistance to said chemotherapeutic agent; and    assessing efficacy of said chemotherapeutic agent based upon results of said conducting and detecting steps.    
     
     
         2 . The method of  claim 1 , wherein said sample of cells in said conducting step comprise malignant cells.  
     
     
         3 . The method of  claim 1 , wherein said sample of cells in said conducting step comprise abnormal proliferating cells.  
     
     
         4 . The method of  claim 1 , wherein said cellular phenotype is cell growth rate or death.  
     
     
         5 . The method of  claim 1 , wherein said genotypic change is a genetic polymorphism or mutation.  
     
     
         6 . The method of  claim 1 , wherein said determining step comprises sequencing a portion of the genome of cells from said patient  
     
     
         7 . The method of  claim 6 , wherein said sequencing is conducted through hybridization or restriction sequencing techniques.  
     
     
         8 . The method of  claim 1 , wherein said determining step comprises comparing said genotype characteristic to a database of genotype characteristics associated with resistance to or altered disposition of said chemotherapeutic agent.  
     
     
         9 . A method for selecting a chemotherapeutic agent for treating a patient, the method comprising: 
 conducting an assay to determine whether a chemotherapeutic agent effects cellular phenotype of a sample of cells from a patient;    determining whether cells from said patient comprise a genotypic characteristic associated with resistance to said chemotherapeutic; and    selecting said chemotherapeutic agent for treating said patient if said chemotherapeutic agent effects cellular phenotype of said sample of cells in said conducting step and if said cells in said determining step do not comprise a genotypic characteristic associated with resistance to said chemotherapeutic agent.    
     
     
         10 . The method of  claim 9 , wherein said sample of cells in said conducting step comprise malignant cells.  
     
     
         11 . The method of  claim 9 , wherein said sample of cells in said conducting step comprise abnormal proliferating cells.  
     
     
         12 . The method of  claim 9 , wherein said cellular phenotype is cell growth rate or death.  
     
     
         13 . The method of  claim 9 , wherein said genotypic change is a genetic polymorphism or mutation.  
     
     
         14 . The method of  claim 9 , wherein said determining step comprises sequencing a portion of the genome of cells from said patient  
     
     
         15 . The method of  claim 14 , wherein said sequencing is accomplished through hybridization or restriction sequencing techniques.  
     
     
         16 . The method of  claim 9 , wherein said determining step comprises comparing said genotype characteristics to a database of genotype characteristics associated with resistance to or altered disposition of said chemotherapeutic agent.  
     
     
         17 . A method for assessing efficacy of a chemotherapeutic agent on malignant cells in a patient, the method comprising: 
 exposing malignant cells from a patient to a chemotherapeutic agent;    conducting an assay to determine whether said chemotherapeutic agent effects cellular phenotype of said malignant cells from said patient;    determining whether a sample of cells from said patient comprise a genotypic characteristic associated with resistance to said chemotherapeutic agent; and    assessing efficacy of said chemotherapeutic agent on said malignant cells from said patient based upon results of said conducting and detecting steps.    
     
     
         18 . The method of  claim 17 , further comprising: 
 selecting said chemotherapeutic agent for treating said patient if said chemotherapeutic agent effects cellular phenotype of said malignant cells in said conducting step and if said cells in said determining step do not comprise a genotypic characteristic associated with resistance to said chemotherapeutic agent.    
     
     
         19 . The method of  claim 17 , wherein said malignant cells are obtained from a tumor specimen from said patient.  
     
     
         20 . The method of  claim 17 , wherein said cells in said determining step are obtained from a blood sample from said patient.  
     
     
         21 . The method of  claim 17 , wherein said cells in said determining step are obtained from a buccal smear from said patient.  
     
     
         22 . The method of  claim 17 , wherein said cellular phenotype is cell growth rate or death.  
     
     
         23 . The method of  claim 17 , wherein said genotypic change is a genetic polymorphism or mutation.  
     
     
         24 . The method of  claim 17 , wherein said determining step comprises sequencing a portion of the genome of cells from said patient  
     
     
         25 . The method of  claim 24 , wherein said sequencing is accomplished through hybridization or restriction sequencing techniques.  
     
     
         26 . The method of  claim 17 , wherein said determining step comprises comparing said genotype characteristics to a database of genotype characteristics associated with resistance to or altered disposition of said chemotherapeutic agent.