""""""""Studies in this area have focused on the characterization of mRNA and protein expression of genes involved in the rate-limiting step of nucleotide excision repair (NER) in human ovarian cancer. These studies have been supplemented by studies of NER modulation in vitro. Generally, the following observations have been made during the past year: 1) ERCC1 appears to be the key gene within the NER process, in human ovarian cancer cells and tissues; 2) A key regulatory factor is AP1, which appears to control upregulation of ERCC1; 3) Pharmacologic and molecular tools can be used to modulate AP1 activity, and ERCC1 levels; 4) The modulation of AP1 and of ERCC1 are directly related to cisplatin-DNA adduct repair, and to cellular sensitivity to platinum compounds; and, 5) Proteasome modulation also dramatically affects ERCC1 and cisplatin-DNA adduct repair."""""""" """"""""This work has been extended to support a prospective randomized clinical trial in advanced stage ovarian cancer. This study is being conducted by the Gynecologic Oncology Group, and involves more than 300 patients. Early data show a direct relationship between platinum-DNA adduct levels in peripheral blood wbc's and disease free survival. Data regarding mRNA expression levels of ERCC1 are pending.""""""""
