The present studies examine the mechanisms by which cancer cells develop resistant to cancer chemotherapeutic drugs and seek to devise methods to overcome this resistance. The phase II drug detoxifying enzyme, glutathione S transferase Pi (GST-Pi) has been previously reported to be over-expressed in several drug resistant tumor cell lines. Monoclonal antibodies to GST-Pi have been prepared, characterized and the distribution of GST-Pi determined in normal and neoplastic tissues. GST-Pi appears to be a useful immunohistological marker in cancers of the uterine cervix and in gliomas. A multimodal approach to cancer treatment has been investigated by the screening of combinations of chemotherapeutic drugs, biologicals and immunotoxins. Human colon carcinoma cell lines have shown greater susceptibility to combinations of 5-fluorouracil and gamma-interferon or tumor necrosis factor than any of these agents alone. It is anticipated that these studies will have an important impact on cancer therapy by increasing our understanding of how tumor cells resist therapeutic intervention.
