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.

1 - 12 . (canceled) 
     
     
         13 . A method of treating a human patient comprising:
 (1) identifying said patient as a candidate for a treatment regimen comprising a pharmaceutically effective amount of an ErbB2-targeting anti-cancer agent chosen from the group consisting of trastuzumab and an inhibitor of a PI3K family protein;   (2) assaying a sample obtained from said patient to
 (a) measure the expression level of PTEN transcript or any complementary DNA derived therefrom by measuring from said sample the level of nucleic acid comprising at least 30 contiguous nucleotides of SEQ ID NO:1 or its complementary RNA; or 
 (b) measure the genomic copy number of a PTEN gene encoding the amino acid sequence of SEQ ID NO:2 in cells of said sample; and 
   (3) administering said treatment regimen based at least in part on said assaying step detecting (a) low or absent PTEN transcript expression in said sample, or (b) deletion of at least one allele of said PTEN gene in said sample.   
     
     
         14 . The method of  claim 13 , wherein said identifying step comprises determining ErbB2 status in a sample from said patient. 
     
     
         15 . The method of  claim 14 , wherein determining ErbB2 status in a sample from said patient comprises determining whether cells in said sample have increased ErbB2 gene expression, increased ErbB32 protein expression, increased ErbB2 gene copy number, or any combination thereof. 
     
     
         16 . The method of  claim 14 , wherein assaying said sample comprises measuring the expression level of PTEN transcript or any complementary DNA derived therefrom by measuring from said sample the level of nucleic acid comprising at least 30 consecutive nucleotides of SEQ ID NO:1 or its complementary RNA. 
     
     
         17 . The method of  claim 16 , wherein said sample is contacted with an oligonucleotide comprising at least 30 consecutive nucleotides of SEQ ID NO:1 or its complement. 
     
     
         18 . The method of  claim 14 , wherein assaying said sample comprises determining the genomic copy number of a PTEN gene encoding the amino acid sequence of SEQ ID NO:2 in cells of said sample. 
     
     
         19 . The method of  claim 18 , wherein the genomic copy number of said PTEN gene in said sample is determined using a fluorescence in situ hybridization assay. 
     
     
         20 . The method of either  claim 13  or  claim 14 , wherein said ErbB2-targeting anti-cancer agent is trastuzumab. 
     
     
         21 . The method of either  claim 13  or  14 , wherein said ErbB2-targeting anti-cancer agent is an inhibitor of a PI3K family protein. 
     
     
         22 . The method of  claim 21 , wherein said inhibitor of a PI3K family protein is chosen from the group consisting of LY294002, Wortmannin, demethoxyviridin, Perifosine, SAR245408 (XL147), BKM120, BEZ235, GS-1101 (CAL-101), PX-866, IPI-145, and BAY 80-6946.