Gene and protein expression profiles associated with the therapeutic efficacy of EGFR-TK inhibitors

Abstract

The present invention provides protein and gene expression profiles indicative of whether a patient afflicted with non-small cell lung cancer is likely to be responsive to treatment with a therapeutic compound that is a EGFR-TK inhibitor. 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 protein expression profiles, and assays for identifying the presence of a gene or protein expression profile in a patient sample.

1 . A gene expression profile for determining if a patient is a responder to treatment with an EGFR-TK inhibitor comprising one or more proteins selected from the group consisting of: p70S6K, phospho-p70S6, phospho-S6, phospho-AKT, phospho-mTOR, phospho-pTEN, phospho MEK, phospho MAPK, phospho-IGFR/InR, EGFR, phosho-EGFR, phospho-HER2 (ErbB2), phospho-ER, phospho-AR, AIK, osteopontin, MMP11 and GFAP. 
     
     
         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 TRFC. 
     
     
         4 . A method of determining if a patient is a responder to treatment with an EGFR-TK inhibitor comprising:
 a. obtaining lung cancer tissue from at least one patient diagnosed with NSCLC; and   b. determining the presence or absence in the sample of a gene expression profile wherein at least about four genes selected from the group consisting of: p70S6K, phospho-S6, phospho-AKT, phospho-mTOR, phospho-pTEN, EGFR, phospho-ER, phospho-AR, AIK, osteopontin, MMP11 and GFAP are up-regulated, and phospho-p70S6, phospho MEK, phospho MAPK, phospho-IGFR/InR, phospho-EGFR and phospho-HER2 (ErbB2) are down-regulated.   
     
     
         5 . The method of  claim 4  further comprising at least one reference gene. 
     
     
         6 . A method of determining if a patient is a responder to treatment with an EGFR-TK inhibitor comprising:
 a. obtaining lung cancer tissue from at least one patient diagnosed with NSCLC; 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: p70S6K, phospho-S6, phospho-AKT, phospho-mTOR, phospho-pTEN, EGFR, phospho-ER, phospho-AR, AIK, osteopontin, MMP11 and GFAP are up-regulated, and phospho-p70S6, phospho MEK, phospho MAPK, phospho-IGFR/InR, phospho-EGFR and phospho-HER2 (ErbB2) are down-regulated.   
     
     
         7 . The method of  claim 7  further comprising at least one reference protein. 
     
     
         8 . The method of  claim 7  wherein step (b) is performed using immunohistochemistry.