Diagnostic and therapeutic methods and compositions involving pten and breast cancer

Abstract

Patients with ErbB2-overexpressing cancers can be given an ErbB2 targeting agent as a therapeutic regimen but not all patients are responsive. The present invention concerns the diagnostic, prognostic and therapeutic methods and compositions for evaluating potential efficacy of an ErbB2 targeting agent in an ErbB2-overexpressing cancers by evaluating PTEN expression, which is predictive of responsiveness or resistance to ErbB2 targeting agents such as trastuzumab. Low PTEN expression is predictive of a patient who will respond poorly to trastuzumab.

What is claimed is: 
     
         1 . A method of determining whether a patient has a lower probability of response to treatment comprising an ErbB2-targeting anti-cancer agent, the method comprising: determining the PTEN nucleic acid status of a sample obtained from said patient and correlating PTEN negative or PTEN low status to a lower probability of response to said treatment. 
     
     
         2 . The method of  claim 1 , wherein determining the PTEN nucleic acid status of said sample comprises determining the expression level of PTEN transcript in said sample. 
     
     
         3 . The method of  claim 2 , wherein said sample is contacted with an oligonucleotide hybridizing under high stringency conditions to a PTEN transcript or a complementary DNA derived therefrom. 
     
     
         4 . The method of  claim 1 , wherein determining the PTEN nucleic acid status of said sample comprises determining the genomic copy number of PTEN in said sample. 
     
     
         5 . The method of  claim 1 , wherein determining the PTEN nucleic acid status of said sample comprises determining whether cells in said sample have mutations in PTEN. 
     
     
         6 . The method of  claim 1 , wherein said ErbB2-targeting anti-cancer agent is trastuzumab. 
     
     
         7 . The method of  claim 1 , wherein said patient's cancer overexpresses ErbB2. 
     
     
         8 . The method of  claim 1 , further comprising determining ErbB2 status in a sample from said patient. 
     
     
         9 . The method of  claim 8 , wherein determining ErbB2 status in a sample from said patient comprises determining whether cells in said sample have increased ErbB2 gene expression, increased ErbB2 protein expression, increased ErbB2 gene copy number, or any combination thereof. 
     
     
         10 . A method of treating a patient comprising identifying said patient as a candidate for a treatment regimen comprising an ErbB2-targeting anti-cancer agent, determining the PTEN nucleic acid status of a sample obtained from said patient, and administering said treatment regimen if said sample is determined to have PTEN negative or PTEN low status. 
     
     
         11 . The method of  claim 10 , wherein identifying said patient as a candidate for a treatment regimen comprising an ErbB2-targeting anti-cancer agent comprises determining ErbB2 status in a sample from said patient. 
     
     
         12 . The method of  claim 11 , wherein determining the status of ErbB2 in a sample from said patient comprises determining whether cells in said sample have increased ErbB2 gene expression, increased ErbB2 protein expression, increased ErbB2 gene copy number, or any combination thereof.