Treatment of Cancers Expressing p95 ErbB2

Abstract

The truncated ErbB2 receptor (p95 ErbB2 ) is shown to differ from the full-length ErbB2 receptor in its association with other ErbB receptors. The truncated receptor preferentially associated with ErbB3, whereas full length ErbB2 heterodimerizes with either EGFR or ErbB3. Consistent with p95 ErbB2 heterodimerization with ErbB3, it is shown that heregulin (an ErbB3 ligand) stimulates p95 ErbB2 phosphorylation in breast cancer cell lines. Described herein are methods of identifying patients suitable for treatment with a p95 ErbB2 inhibitor, and methods of treating such patients.

1 . A method of treating a human patient having a solid tumor comprising the steps of:
 obtaining at least one sample from said patient,   testing for the presence of p95 ErbB2  in said sample; and   treating said patient with at least one compound that inhibits p95 ErbB2  if p95 ErbB2  is detected in said sample.   
     
     
         2 . The method of  claim 1 , wherein said tumor is selected from breast, ovarian, colon, head and neck, bladder, renal, and lung. 
     
     
         3 . The method of  claim 1 , wherein said tumor is a breast tumor. 
     
     
         4 . The method of  claim 1 , wherein said sample is a tumor sample. 
     
     
         5 . The method of  claim 1 , wherein said sample is a blood sample. 
     
     
         6 . The method of  claim 1  wherein said at least one compound inhibits both p95 ErbB2  and p185 ErbB2 . 
     
     
         7 . The method of  claim 1 , further comprising treating said patient with a second compound that inhibits either p95 ErbB2  or p185 ErbB2 . 
     
     
         8 . The method of  claim 1 , wherein said at least one compound is GW572016. 
     
     
         9 . The method of  claim 7 , wherein second compound is trastuzumab. 
     
     
         10 . The method of  claim 1 , wherein the expression of p95 ErbB2  is determined by an immunohistochemical method. 
     
     
         11 . The method of  claim 1 , wherein the expression of p95 ErbB2  is determined by measuring ErbB2 extracellular domain in a sample of a subject's serum. 
     
     
         12 . The method of  claim 4 , wherein said tumor sample is selected from, breast, ovarian, colon, head and neck, bladder, renal, and lung. 
     
     
         13 . The method of  claim 1 , wherein said tumor is a solid epithelial tumor. 
     
     
         14 . The method of  claim 12 , wherein said tumor is a breast tumor. 
     
     
         15 . The method of  claim 1 , wherein said human has previously been treated with trastuzumab. 
     
     
         16 . A method of  claim 1 , wherein the presence of p95 ErbB2  level is at least 5% of full-length ErbB2 receptor level in said sample. 
     
     
         17 . A method of treating a human patient for breast cancer, comprising the steps of
 obtaining at least one sample from said patient;   testing for expression of p95 ErbB2  in said sample; and   treating said patient with a GW572016 if p95 ErbB2  is detected in said sample.   
     
     
         18 . A method of treating a human subject having a solid tumor that overexpresses ErbB2, said method comprising
 determining whether said solid tumor exhibits trastuzumab resistance, treating said patient with GW572016 if said tumor is trastuzumab resistant.   
     
     
         19 . A method of  claim 18  wherein said tumor expresses p95 ErbB2  at a level at least equal to about 5%, 10%, 20%, 25% or more of full-length ErbB2 receptor expression level. 
     
     
         20 . A method of selecting therapy for a human subject having a solid tumor that overexpresses ErbB2, said method comprising:
 determining whether said solid tumor expresses p95 ErbB2 ,   correlating the measurement of p95 ErbB2  expression with an improved likelihood of response to a p95 ErbB2  inhibitor wherein expression of p95 ErbB2  is at least 5% of full-length ErbB2 expression.