Simple SummaryOvarian cancer remains the deadliest cancer of the female reproductive system. There is a significant body of evidence that has demonstrated that Signal Transducers and Activators of Transcription (STATs) play a critical role in ovarian cancer progression. STAT proteins are highly activated in ovarian cancer and are thus attractive targets for developing targeted therapeutic strategies. This review highlights the current knowledge of STAT biology in ovarian cancer, with an emphasis on epithelial ovarian cancer, while also providing a comprehensive discussion on STAT specific inhibitors in preclinical and clinical stages of development. As a result, this review will be relevant to a wide readership, encompassing aspects of biology and therapeutics.AbstractOvarian cancer (OvCa) is a deadly gynecologic malignancy that presents many clinical challenges due to late-stage diagnoses and the development of acquired resistance to standard-of-care treatment protocols. There is an increasing body of evidence suggesting that STATs may play a critical role in OvCa progression, resistance, and disease recurrence, and thus we sought to compile a comprehensive review to summarize the current state of knowledge on the topic. We have examined peer reviewed literature to delineate the role of STATs in both cancer cells and cells within the tumor microenvironment. In addition to summarizing the current knowledge of STAT biology in OvCa, we have also examined the capacity of small molecule inhibitor development to target specific STATs and progress toward clinical applications. From our research, the best studied and targeted factors are STAT3 and STAT5, which has resulted in the development of several inhibitors that are under current evaluation in clinical trials. There remain gaps in understanding the role of STAT1, STAT2, STAT4, and STAT6, due to limited reports in the current literature; as such, further studies to establish their implications in OvCa are necessitated. Moreover, due to the deficiency in our understanding of these STATs, selective inhibitors also remain elusive, and therefore present opportunities for discovery.