Method for predicting the sensitivity to chemotherapy

Abstract

Herewith described is a novel method for predicting the sensitivity towards chemotherapy, of a patient in need thereof, which comprises obtaining a blood sample from the patient and detecting the levels of blood glutathione (GSH) as a surrogate marker for glutathione-S-transferase (GST) activity in tumor tissues.

1 . A method for predicting the sensitivity towards chemotherapy, of a patient in need thereof, which comprises obtaining a blood sample from the patient and detecting the presence of blood glutathione (GSH) as a surrogate marker for glutathione-S-transferase (GST) activity in tumor tissues.  
     
     
         2 . The method of  claim 1  which allows predicting whether the given tumor is associated with GST over expression.  
     
     
         3 . The method of  claim 2  wherein the tumor is selected from the group consisting of gastrointestinal tumors, uterine and ovarian cancers, head and neck cancer, lung carcinomas, sarcomas, liver tumors, pancreatic cancer, breast cancer, prostate cancer, melanoma and haematological tumors.  
     
     
         4 . The method of  claim 3  wherein the tumor is selected from head, neck and lung cancer.  
     
     
         5 . A method for selecting the proper chemotherapeutic treatment for a patient in need thereof, which first comprises predicting his sensitivity towards chemotherapy by obtaining a blood sample from the patient, detecting the levels of blood glutathione (GSH) as a surrogate marker for glutathione-S-transferase (GST) activity in tumor tissues, determining whether the blood GSH levels fall within a range indicative of a potential for the patient to exhibit de novo or later progression to resistance to anticancer chemotherapeutic agents, and selecting a suitable and effective chemotherapeutic treatment based on the above GSH levels.  
     
     
         6 . The method of  claim 5  for selecting the proper chemotherapeutic treatment for a patient suffering of a tumor selected from the group consisting of gastrointestinal tumors, uterine and ovarian cancers, head and neck cancer, lung carcinomas, sarcomas, liver tumors, pancreatic cancer, breast cancer, prostate cancer, melanoma and haematological tumors  
     
     
         7 . The method of  claim 6  wherein the tumor is selected from head, neck and lung cancer.  
     
     
         8 . The method of  claim 5  which, based on the blood GSH levels, allows to select the proper chemotherapeutic treatment which may comprise the administration to the patient in need thereof of the compound N-(5-{[(5-{[(5-{[(2-{[amino(imino)methyl]amino} ethyl)amino]carbonyl}-1-methyl-1H-pyrrol-3-yl)amino] carbonyl}-1-methyl-1H-pyrrol-3-yl)amino]carbonyl}-1-methyl-1H-pyrrol-3-yl)- 4 -[(2-bromoacryloyl)amino]-1-methyl-1H-pyrrole-2-carboxamide (internal code PNU 166196) or a pharmaceutically acceptable salt thereof or, alternatively, of a conventional antitumor agent.  
     
     
         9 . The method of  claim 8  wherein the conventional antitumor agent is selected from the group consisting of alkylating agents, anthracyclines and platinum derivatives.  
     
     
         10 . A method for treating a patient suffering from a tumor over-expressing the GSH/GST system, which first comprises predicting his sensitivity towards chemotherapy by obtaining a blood sample from the patient, detecting the levels of blood GSH as a surrogate marker for GST activity in tumor tissues, determining whether the GSH levels fall within a range indicative of a potential for the patient to exhibit de novo or later progression to resistance to chemotherapeutic agents, and selecting a suitable and effective chemotherapeutic treatment based on the above GSH/GST levels which treatment may comprise the administration of an effective amount of N-(5-{[(5-{[(5-{[(2-{[amino(imino)methyl]amino} ethyl)amino]carbonyl}-1-methyl-1H-pyrrol-3-yl)amino]carbonyl}-1-methyl-1H-pyrrol-3-yl)amino]carbonyl}-1-methyl-1H-pyrrol-3-yl)- 4 -[(2-bromoacryloyl)amino]-1-methyl-1H-pyrrole-2-carboxamide (internal code PNU 166196), or of a pharmaceutically acceptable salt thereof.  
     
     
         11 . The method of  claim 10  wherein the tumor is selected from the group consisting of gastrointestinal tumors, uterine and ovarian cancers, head and neck cancer, lung carcinomas, sarcomas, liver tumors, pancreatic cancer, breast cancer, prostate cancer, melanoma and haematological tumors.  
     
     
         12 . The method of  claim 11  wherein the tumor is selected from head, neck and lung cancer.  
     
     
         13 . Use of a kit for determining blood GSH levels as a surrogate marker for GST activity in tumor tissues.