The objective of the research is to measure the DNA repair protein 06- alkylguanine-DNA alkyltransferase in biopsies of metastatic malignant melanoma and correlate those levels with the response of patients to treatment with alkylating nitrosources. These drugs, such as BCNU and DTIC, create cytotoxic DNA damage that is reparable by the transferase, and therefore the DNA repair capacity may be a measure of drug resistance. In this retrospective study, slides will be collected from archived tumor blocks from patients who have already been treated, and the levels of transferase measured using monoclonal antibodies against the transferase and quantitative immunofluorescence microscopy. After measurement of alkyltransferase, patient response data will be returned, and the clinical response correlated with transferase levels. Correlation of low transferase levels with positive response to chemotherapy will demonstrate the prognostic value of transferase measurements in metastatic malignant melanoma. This research is innovative in that it applies a basic science mechanism of DNA damage by chemotherapy and DNA repair by transferase to the clinical setting of drug resistance in metastatic melanoma. The results of this research will lead to the commercial development of a diagnostic test used in selection of the most appropriate adjuvant chemotherapy in this disease. PROPOSED COMMERCIAL APPLICATION: The research will lead to a central station diagnostic test used to the time of tumor biopsy to measure the level of transferase in tumor tissue. This test will be used to predict the response of patients to alkylation chemotherapy of melanoma.
Thesaurus Terms:carmustine, dacarbazine, drug adverse effect, neoplasm /cancer chemotherapy, nitrosourea biopsy, clinical research, fluorescence microscopy, human subject, human tissue, image processing, immunofluorescence technique, monoclonal antibody, tissue /cell cultureNational Cancer Institute (NCI)
