Detection of met amplification to predict responsiveness of cancer to drugs

Abstract

The present invention provides a novel method to determine the likelihood of effectiveness of a treatment in an individual affected with or at risk for developing cancer. The method involves detecting the presence or absence of Met amplification in an individual. The presence of Met amplification indicates that a Met targeting treatment is likely to be effective. Preferably, the Met targeting treatment is PHA-665752 or PF-02341066. In addition, the present methods allow for the detection of cancer in an individual, wherein the presence of Met amplification indicates that cancer is present and further that it will be treatable, namely with a Met targeting treatment.

1 . A method for identifying a cancer in an individual that is susceptible to treatment with a Met tyrosine kinase inhibitor comprising:
 a) obtaining a fixed tissue sample comprising genomic DNA from an individual;   b) contacting the tissue sample with a detectable nucleic acid probe that specifically hybridizes to Met gene DNA to thereby form a hybridization complex comprising the nucleic acid probe and the Met gene DNA;   c) measuring amplification of the Met gene in the tissue sample by detecting a signal from the probe in the hybridization complex and comparing to that of a control sample, with amplification being a minimum of about an 8-fold increase in Met gene copy number compared to a non-amplified copy number;   d) identifying the cancer as susceptible to treatment when Met gene amplification is measured in the tissue sample, and identifying the cancer as resistant in the absence of Met gene amplification in the tissue sample; and   e) administering a Met tyrosine kinase inhibitor to the individual if a minimum of about an 8-fold increase in Met gene copy number is measured in the tissue sample.   
     
     
         2 . The method of  claim 1 , wherein the measuring is by PCR, qPCR, RT-PCR, Southern Blot, comparative genomic hybridization, microarray based comparative genomic hybridization, fluorescence in situ hybridization (FISH), ligase chain reaction (LCR), or LAMP. 
     
     
         3 . The method of  claim 1 , wherein the cancer is selected from the group consisting of gastrointestinal cancer, prostate cancer, ovarian cancer, breast cancer, head and neck cancer, lung cancer, non-small cell lung cancer, cancer of the nervous system, kidney cancer, retina cancer, skin cancer, liver cancer, pancreatic cancer, genital-urinary cancer, esophageal cancer and bladder cancer. 
     
     
         4 . The method of  claim 1 , wherein the Met tyrosine kinase inhibitor is PHA-665752 or PF-02341066. 
     
     
         5 . A method for identifying a cancer in an individual that is susceptible to treatment with a Met tyrosine kinase inhibitor comprising:
 a) obtaining a fixed tissue sample comprising genomic DNA from an individual;   b) contacting the sample with a detectable antibody or antibody fragment probe that specifically binds to a duplex comprising Met genomic DNA to thereby form a complex;   c) measuring amplification of the Met gene in the tissue sample by detecting a signal from the probe in the complex and comparing to that of a control sample, with amplification being a minimum of about an 8-fold increase in Met gene copy number compared to a non-amplified copy number;   d) identifying the cancer as susceptible to treatment when Met gene amplification is measured in the tissue sample, and identifying the cancer as resistant in the absence of Met gene amplification in the tissue sample; and   e) administering a Met tyrosine kinase inhibitor to the individual if a minimum of about an 8-fold increase in Met gene copy number is measured in the tissue sample.   
     
     
         6 . The method of  claim 5 , wherein the measuring is by immunohistochemistry (IHC). 
     
     
         7 . The method of  claim 5 , wherein the cancer is selected from the group consisting of gastrointestinal cancer, prostate cancer, ovarian cancer, breast cancer, head and neck cancer, lung cancer, non-small cell lung cancer, cancer of the nervous system, kidney cancer, retina cancer, skin cancer, liver cancer, pancreatic cancer, genital-urinary cancer, esophageal cancer and bladder cancer. 
     
     
         8 . The method of  claim 5 , wherein the Met tyrosine kinase inhibitor is PHA-665752 or PF-02341066.