Biomarkers and methods for determining sensitivity to epidermal growth factor receptor modulators

Abstract

EGFR biomarkers useful in a method for predicting the likelihood that a mammal that will respond therapeutically to a method of treating cancer comprising administering an EGFR modulator, wherein the method comprises (a) measuring in the mammal the level of at least one biomarker selected from epiregulin and amphiregulin, (b) exposing a biological sample from the mammal to the EGFR modulator, and (c) following the exposing of step (b), measuring in the biological sample the level of the at least one biomarker, wherein an increase in the level of the at least one biomarker measured in step (c) compared to the level of the at least one biomarker measured in step (a) indicates an increased likelihood that the mammal will respond therapeutically to the method of treating cancer.

1 - 10 . (canceled) 
     
     
         11 . A method for predicting the likelihood a colorectal cancer patient will respond therapeutically to a method of treating colorectal cancer with a therapy that comprises administering an anti-EGFR antibody that inhibits binding of EGF to EGFR, wherein the method for predicting comprises measuring the mRNA expression level of both epiregulin and amphiregulin biomarkers in a colorectal cancer sample of said patient,
 wherein an elevated level of said biomarkers in a colorectal cancer sample relative to a predetermined level of said biomarkers indicates an increased likelihood said patient will respond therapeutically to said method of treating colorectal cancer.   
     
     
         12 . The method of  claim 11  further comprising the step of measuring at least one additional biomarker selected from Table 1. 
     
     
         13 . The method of  claim 11  wherein said colorectal cancer sample is a tissue sample comprising colorectal cancer cells and said tissue is fixed; paraffin-embedded; fixed and paraffin-embedded; formalin-fixed and paraffin-embedded; formaldehyde-fixed and paraffin-embedded; in fresh, or frozen. 
     
     
         14 . The method according to  claim 11  wherein said mRNA expression measurement is performed using a method selected from the group consisting of: (a) PCR; (b) RT-PCR; (c) microarray; (d) immunohistochemistry; (e) in situ hybridization; (f) array hybridization; (g) Northern blot; (h) dot-blot; and (i) RNAse protection assay. 
     
     
         15 . The method of  claim 11  further comprising the step of determining whether said colorectal cancer sample has the presence of a mutated K-RAS, wherein detection of a mutated K-RAS indicates a decreased likelihood said patient will respond therapeutically to said method of treating colorectal cancer. 
     
     
         16 . The method of  claim 11  further comprising the step of determining whether said colorectal cancer sample has the presence of wild-type K-RAS, wherein detection of wild-type K-RAS indicates an increased likelihood said patient will respond therapeutically to said method of treating colorectal cancer. 
     
     
         17 . The method according to  claim 11 , wherein said anti-EGFR antibody is selected from the group consisting of: a monoclonal, polyclonal or single chain antibody. 
     
     
         18 . The method of  claim 11 , wherein said anti-EGFR antibody is cetuximab. 
     
     
         19 . The method according to  claim 11 , wherein said anti-EGFR antibody is panitumumab. 
     
     
         20 . The method according to  claim 11 , further comprising the step of administering said anti-EGFR antibody to said patient if the level of said biomarkers is increased relative to a predetermined level of said biomarkers in a colorectal cancer sample, wherein said anti-EGFR antibody inhibits binding of EGF to EGFR. 
     
     
         21 . The method according to  claim 18 , further comprising the step of administering said anti-EGFR antibody to said patient if the level of said biomarkers is increased relative to a predetermined level of said biomarkers in a colorectal cancer sample, wherein said anti-EGFR antibody inhibits binding of EGF to EGFR. 
     
     
         22 . The method according to  claim 19 , further comprising the step of administering said anti-EGFR antibody to said patient if the level of said biomarkers is increased relative to a predetermined level of said biomarkers in a colorectal cancer sample, wherein said anti-EGFR antibody inhibits binding of EGF to EGFR. 
     
     
         23 . A method for predicting the likelihood a colorectal cancer patient will respond therapeutically to a method of treating colorectal cancer with an EGFR modulator that inhibits binding of EGF to EGFR, comprising:
 (a) measuring the mRNA expression level of both epiregulin and amphiregulin biomarkers in a colorectal cancer sample of said patient; and   (b) administering a therapy comprising cetuximab to said patient if said measuring step indicates said patient has an elevated level of said biomarkers in said colorectal cancer sample relative to a predetermined level.   
     
     
         24 . A method for predicting the likelihood a colorectal cancer patient will respond therapeutically to a method of treating colorectal cancer with an EGFR modulator that inhibits binding of EGF to EGFR, comprising:
 (a) measuring the mRNA expression level of both epiregulin and amphiregulin biomarkers in a colorectal cancer sample of said patient; and   (b) administering a therapy comprising panitumumab to said patient if said measuring step indicates said patient has an elevated level of said biomarkers in said colorectal cancer sample relative to a predetermined level.