Nitrosoureas are effective antitumor agents, especially in brain cancer. However, tumors are often resistant due to activity of the human DNA repair enzyme, O6-methylguanine-DNA methyltransferase (06MT) The outcome of chemotherapy may be predicted by measuring the levels of 06MT in single cells from tumor biopsies, and a morerational treatment regime may be designed. This approach is now feasible because of the cloning of the human 06MT gene. The Phase I research will use polyclonal antibodies and DNA probes to measure 06MT levels in human tumor samples taken at initial biopsy and at second-look surgery. The immunohistochemical and in situ hybridization assay will be developed, and test results will be correlated with patient outcome. This will establish the usefulness of these assays in a clinical trial to predict drug resistance and patient response to treatmentAwardee's statement of the potential commercial applications of the research:These assays may be developed into a diagnostic test to predict the outcome of chemotherapy. The test may be performed at a central station or sold as kits. The test is important at least to all brain cancer patients and potentially to many other cancer patientsNational Cancer Institute (NCI)
