Chemotherapy has proven useful in the management of many different types of cancers. However, two major impediments to effective chemotherapy are the inability to predict which patients would respond to a given drug regimen and the development of multiple drug resistance in a large number of cancer patients who initially respond well to chemotherapy. Diagnostic reagents that would be able to determine if and when a patient developed drug resistance, as well as reagents capable of predicting the responsiveness of an individual patient to a given chemotherapeutic regimen prior to treatment, would greatly expand the utility of available anticancer drugs. The primary goal of this project is to develop sensitive immunological reagents capable of quantitating and identifying the amount of topoisomerase II present in a cancerous cell. Because the amount of topoisomerase II present in a cell is well correlated with the therapeutic utility of many anticancer drugs, these monoclonal antibodies will be useful in prescribing and monitoring the effectiveness of a chemotherapeutic regimen. Additionally, since in some cases alterations in topoisomerase II are responsible for drug resistance, antibodies that can identify cancer cells that contain drug-resistant topoisomerase II will also be developed. These antibodies would be formatted to develop immunological tests capable of quantitating levels of topoisomerase II as a medical and basic research toolAwardee's statement of the potential commercial applications of the research:Monoclonal antibodies produced in Phase I would serve as diagnostic tools capable of quantitating and identifyingtopoisomerase II in cancerous cells as an aid in prescribing and monitoring the utility of chemotherapeutic regimens. These antibodies would also serve as basic research tools in characterizing the role of topoisomerases in normal and transformed cellsNational Cancer Institute (NCI)
