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 screening a human subject in need of treatment for a solid epithelial tumor that overexpresses p185 ErbB2 , as an aid in selecting therapy, comprising determining whether the tumor expresses p95 ErbB2 , where expression of p95 ErbB2  indicates said subject is more likely to exhibit a favorable clinical response to treatment that includes GW572016, than to treatment that does not include GW572016.  
     
     
         2 . A method according to  claim 1  where expression of p95 ErbB2  in tumor tissue is assessed by immunohistochemical methods.  
     
     
         3 . A method according to  claim 1  where expression of p95 ErbB2  is assessed by measuring ErbB2 extracellular domain (ECD) in a sample of the subject's serum.  
     
     
         4 - 5 . (canceled)  
     
     
         6 . A method according to  claim 1  where said tumor is selected from breast, ovarian, colon, head and neck, bladder, renal cell and lung tumors.  
     
     
         7 . A method according to  claim 1  where said subject has breast cancer.  
     
     
         8 . A method according to  claim 1  where said subject has previously been treated with a p185 ErbB2  inhibitor.  
     
     
         9 . A method according to  claim 1  where said subject has previously been treated with trastuzumab.  
     
     
         10 . A method of treating a subject with a solid epithelial tumor that overexpresses p185 ErbB2 , comprising determining whether the tumor expresses p95 ErbB2 , and treating said subject with GW572016 if said tumor expresses p95 ErbB2 .  
     
     
         11 . A method according to  claim 10  where expression of p95 ErbB2  in tumor tissue is assessed by immunohistochemical methods.  
     
     
         12 . A method according to  claim 10  where expression of p95 ErbB2  is assessed by measuring ErbB2 extracellular domain (ECD) in the subject's serum.  
     
     
         13 .- 14 . (canceled)  
     
     
         15 . A method according to  claim 10  where said tumor is selected from breast, ovarian, colon, head and neck, bladder, renal cell and lung tumors.  
     
     
         16 . A method according to  claim 10  where said subject has breast cancer.  
     
     
         17 . A method according to  claim 10  where said subject has previously been treated with a p185 ErbB2  inhibitor.  
     
     
         18 . A method according to  claim 10  where said subject has previously been treated with trastuzumab.  
     
     
         19 . (canceled)  
     
     
         20 . A method of treating a subject with a solid epithelial tumor that expresses p95 ErbB2 , comprising administering a therapeutically effective amount of GW572016 to said subject.  
     
     
         21 . A method according to  claim 20 , where said subject has breast cancer.  
     
     
         22 . (canceled)  
     
     
         23 . A method according to  claim 20  where said subject has previously been treated with trastuzumab.  
     
     
         24 . A method of treating a subject with breast cancer that is resistant to treatment with a p185 ErbB2  inhibitor that binds to the extracellular domain of ErbB2 and whose tumor expresses p95 ErbB2 , comprising administering a therapeutically effective amount of a p95 ErbB2  inhibitor to said subject.  
     
     
         25 . (canceled)  
     
     
         26 . A method according to  claim 24  where said subject has previously been treated with trastuzumab.  
     
     
         27 . A method of screening a subject in need of treatment for breast cancer to determine suitability for treatment with a p185 ErbB2  inhibitor that binds to the extracellular domain of ErbB2, comprising determining whether said tumor expresses an elevated level of p95 ErbB2 , where an elevated level of p95 ErbB2  indicates that said subject should not be treated with a p185 ErbB2  inhibitor in the absence of treatment with a p95 ErbB2  inhibitor.  
     
     
         28 . A method according to  claim 27 , further comprising treating said subject with a treatment selected from (a) a p185 ErbB2  inhibitor, (b) a combined a p185 ErbB2  inhibitor and GW572016.