The present studies examine the mechanisms by which cancer cells develop resistance 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 an extremely useful immuno-histological marker in cancers of the uterine cervix and may also be a marker for colon cancer. In addition to the above studies, a multimodal approach to cancer treatment has been investigated by the analysis of the effects of combinations of chemotherapeutic drugs, biologicals and immunotoxins on human tumor cell lines. Human colon, ovarian, and myeloma tumor cell lines resistant to chemotherapeutic drugs have been developed by in vivo passage in nude mice or in vitro culturing. These cell lines are being utilized to analyze the effects of biological response modifiers (e.g. IL-6) on the drug resistance phenotype and growth characteristics of these cells.
