Gene and protein expression profiles associated with the therapeutic efficacy of irinotecan

Abstract

The present invention includes gene and protein expression profiles indicative of whether a cancer patient is likely to respond to treatment with irinotecan. By identifying such responsiveness, a treatment provider may determine in advance those patients who would benefit from such treatment, as well as identify alternative therapies for non-responders. The present invention further provide methods of using the gene and/or protein expression profiles and assays for identifying the presence of a gene and/or protein expression profile in a patient sample.

1 . A gene expression profile for determining if a patient is a responder to treatment with irinotecan comprising at least about four or more genes selected from the group consisting of: ERBB2, GRB7, Erk1 kinase, JNK1 kinase, BCL2, MK167, phospho-Akt, CD68, BAG1, phospho-GSK-3beta, MMP11, CTSL2, CCNB1, BIRC5, STK6, MRP14 and GSTM1.  
     
     
         2 . The gene expression profile of  claim 1  further comprising at least one reference gene.  
     
     
         3 . The gene expression profile of  claim 2  wherein the reference gene is selected from the group consisting of: ACTB, GAPD, GUSB, RPLP0 and TFRC.  
     
     
         4 . A method of determining if a patient is a responder to treatment with irinotecan comprising: 
 a. obtaining colon cancer tissue from at least one patient diagnosed with colon cancer; and    b. determining the presence or absence in the sample of a gene expression profile wherein at least about four or more genes selected from the group consisting of: ERBB2, GRB7, JNK1 kinase, BCL2, MK167, phospho-Akt, CD68 and BAG1, are up-regulated and Erk1 kinase, phospho-GSK-3beta, MMP11, CTSL2, CCNB1, BIRC5, STK6, MRP14 and GSTM1 are down-regulated.    
     
     
         5 . The method of  claim 1  further comprising at least one reference gene.  
     
     
         6 . The method of  claim 5  wherein the reference gene is selected from the group consisting of: ACTB, GAPD, GUSB, RPLP0 and TFRC.  
     
     
         7 . A method of determining if a patient is a responder to treatment with irinotecan comprising: 
 a. obtaining colon cancer tissue from at least one patient diagnosed with colon cancer; and    b. determining the presence or absence in the sample of a protein expression profile wherein at least about four or more proteins selected from the group consisting of: ERBB2, GRB7, JNK1 kinase, BCL2, MK167, phospho-Akt, CD68 and BAG1, are up-regulated and Erk1 kinase, phospho-GSK-3beta, MMP11, CTSL2, CCNB1, BIRC5, STK6, MRP14 and GSTM1 are down-regulated.    
     
     
         8 . The method of  claim 1  further comprising at least one reference protein.  
     
     
         9 . The method of  claim 5  wherein the reference protein is selected from the group consisting of: ACTB, GAPD, GUSB, RPLP0 and TFRC.  
     
     
         10 . The method of  claim 7  wherein step (b) is performed using immunohistochemistry.