Stratification of cancer patients for susceptibility to therapy with PTK2 inhibitors

Abstract

A method for determining whether a cancer patient is susceptible to treatment with a protein tyrosine kinase 2 (PTK2) inhibitor, comprising detecting the expression of the E-cadherin protein in a cancer sample of said cancer patient, wherein an E-cadherin protein immunoreactivity score (IRS) of 0-2 indicates that the cancer patient is susceptible to treatment with a PTK2 inhibitor. The invention further encompasses treatment of a patient with a protein tyrosine kinase 2 (PTK2) inhibitor if it has been so determined that said patient is susceptible to such treatment.

1 . A method of treating a cancer in a cancer patient, said method comprising the following steps:
 (a) determining whether said patient is susceptible to treatment with a protein tyrosine kinase 2 (PTK2) inhibitor by detecting the amount of expression of the E-cadherin protein in a cancer sample taken from said patient, wherein an E-cadherin protein immunoreactivity score (IRS) of 0-2 indicates that the patient is susceptible to treatment with a PTK2 inhibitor; and   (b) treating said patient with a protein tyrosine kinase 2 (PTK2) inhibitor if it has been determined that said patient is susceptible to treatment with a protein tyrosine kinase 2 (PTK2) inhibitor.   
     
     
         2 . The method of  claim 1 , wherein said cancer patient is a mammal. 
     
     
         3 . The method of  claim 2 , wherein said mammal is a human. 
     
     
         4 . The method of  claim 1 , wherein said cancer is a carcinoma. 
     
     
         5 . The method of  claim 1 , wherein said cancer is selected from the group consisting of carcinoma of the duodenum, colon, rectum and anus; carcinoma of the pancreas; carcinoma of the urinary bladder; lung tumours (small-cell lung cancer (SCLC), non-small-cell lung cancer (NSCLC) such as for example squamous cell carcinomas, adenocarcinomas (acinary, papillary, bronchiolo-alveolar) and large-cell bronchial carcinoma (giant cell carcinoma, clear-cell carcinoma)); breast cancer such as ductal, lobular, mucinous or tubular carcinoma, ovarian cancer (ovarian carcinoma—mucinous or serous cystoadenocarcinoma, endometriod carcinoma, and clear cell tumour); head and neck tumours; liver cell carcinoma (hepatocellular carcinoma (HCC); kidney cancer such as for example (clear cell renal cell carcinoma, papillary renal cell carcinoma, chromophobe renal cell carcinoma and collecting duct carcinoma); prostate cancer; and cancer of the vulva. 
     
     
         6 . The method of  claim 1 , wherein said detection of the expression of the E-cadherin protein in a cancer sample of a cancer patient is conducted by way of an immunohistochemistry (IHC) method. 
     
     
         7 . The method of  claim 6 , wherein said IHC method employs a primary antibody which is specific for E-cadherin and a secondary antibody which specifically reacts with the primary antibody. 
     
     
         8 . A method of screening for a therapeutically effective PTK2 inhibitor comprising the following steps:
 (a) providing cancer cells or a cancer cell line which are characterized by an E-cadherin protein immunoreactivity score of 2, 1, or 0 (1 being preferred and 0 being even more preferred)   (b) contacting the cancer cell or the cancer cell line of (a) with a PTK2 inhibitor; and   (c) evaluating whether the PTK2 inhibitor negatively affects the cancer cell/cancer cell lines.