Epithelial ovarian cancers (OC) are highly lethal tumors, but treatment options are limited, largely because our poor understanding of the biology of OC development has hindered the development of new drugs. Recent investigations in our laboratory and others identified the PAX8 gene as a major driver of OC, regulating the expression of key genes to promote tumorigenesis. The goal of this proposal is to understand how DNA mutations impact PAX8-dependent control of target gene expression to promote cancer development. The idea is that by understanding pathways upstream of cancer gene expression we can identify much-needed new therapeutic targets for OC.