Method for predicting response to epidermal growth factor receptor-directed therapy

Abstract

This invention provides methods for determining or predicting response to cancer therapy in an individual.

1 . A method for predicting a response to an epidermal growth factor receptor-directed therapy in a human subject, the method comprising the step of assaying a tumor sample from the human subject before therapy with one or a plurality of reagents that detect expression and/or activation of predictive biomarkers for cancer; and determining a pattern of expression and/or activation of at least two of said predictive biomarkers, wherein the pattern predicts the human subject's response to the epidermal growth factor receptor-directed therapy. 
     
     
         2 . The method of  claim 1 , wherein the predictive biomarker is a growth factor receptor, or a growth factor receptor-related downstream signaling molecule. 
     
     
         3 . The method of  claim 2 , wherein the growth factor receptor is HER1 (EGFR), pHER1, HER2/neu, HER3, or any combination thereof. 
     
     
         4 . The method of  claim 2 , wherein the growth factor receptor-related downstream signaling molecules is pERK. 
     
     
         5 . The method of  claim 2 , wherein the growth factor receptor is HER1 (EGFR), pHER1, HER2/neu, HER3, or any combination thereof, and the growth factor receptor-related downstream signaling molecules is pERK. 
     
     
         6 . The method of  claim 1 , where in the predictive biomarkers are HER1 (EGFR) and HER3. 
     
     
         7 . The method of  claim 6 , wherein when HER1 (EGFR) is undetectable is predictive of the human subject not responding to the epidermal growth factor receptor-directed therapy. 
     
     
         8 . The method of  claim 6 , wherein when HER3 is undetectable is predictive of the human subject responding to the epidermal growth factor receptor-directed therapy. 
     
     
         9 . The method of  claim 1 , where in the predictive biomarkers are HER1 (EGFR) and pERK. 
     
     
         10 . The method of  claim 1 , where in the predictive biomarkers are pERK and HER3. 
     
     
         11 . The method of  claim 1 , where in the predictive biomarkers are HER1 (EGFR), HER3, and pERK. 
     
     
         12 . A method of selecting a subject with cancer for treatment with a molecule targeting epidermal growth factor receptor (EGFR), comprising determining the level of expression of HER3 in a cell or tissue sample from the subject, wherein if the level of HER3 expression is low in the cells, the subject is selected. 
     
     
         13 . The method of  claim 12 , wherein the molecule is an anti-EGFR antibody. 
     
     
         14 . The method of  claim 13 , wherein the antibody is ABX-0303. 
     
     
         15 . The method of  claim 12 , wherein the determining step further comprises determining expression of one or more of HER1 (EGFR), pHER1, HER2/neu, and pERK. 
     
     
         16 . A method of predicting the likely response rate to a molecule targeting epidermal growth factor receptor (EGFR) of a subject having a cancer that overexpresses EGFR, comprising the step of determining the level of expression of HER3 in a cell or tissue sample from the subject, wherein if the level of HER3 expression is low in the cells, the subject is likely to respond to the molecule targeting EGFR. 
     
     
         17 . The method of  claim 16 , wherein the molecule is an anti-EGFR antibody. 
     
     
         18 . The method of  claim 17 , wherein the antibody is ABX-0303. 
     
     
         19 . The method of  claim 16 , wherein the determining step further comprises determining expression of one or more of HER1 (EGFR), pHER1, HER2/neu, and pERK. 
     
     
         20 . A method of selecting a subject with cancer for treatment with a molecule targeting epidermal growth factor receptor (EGFR), the method comprising:
 a) determining an expression and/or activation profile of two or more growth factor receptors in cells and/or tissues of the subject; and   b) selecting the subject based on the expression and/or activation profile,   
       wherein the subject is selected when the level of expression of HER3 is low, the level of expression of the HER1 is high, and/or the level of the pERK index is high. 
     
     
         21 . The method of  claim 20 , wherein the molecule is an anti-EGFR antibody. 
     
     
         22 . The method of  claim 21 , wherein the antibody is ABX-0303. 
     
     
         23 . The method of  claim 22 , wherein the growth factor receptors comprise one or more of HER1 (EGFR), pHER1, HER2/neu, and HER3.