Tryptophan catabolism in epithelial ovarian carcinoma

Ovarian cancers are the most common cause of gynecological death, and the five-year survival rate for women diagnosed with epithelial ovarian carcinoma (EOC) remains extremely low at only 47%. Recent studies have highlighted the importance of the anti-tumor immune response in determining EOC clinical outcomes, and much research is currently being undertaken in an effort to reverse tumor immune evasion. One mechanism known to promote tumor immune evasion in multiple cancer types is tryptophan catabolism. Here we review the potential role of two rate-limiting enzymes that evolved separately to catabolize tryptophan, indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase 2 (TDO2), that may be active in ovarian cancers and result in the production of immune suppressive catabolites. Research to date has focused on IDO inhibitors, currently in clinical trials, but these therapies fail to inhibit TDO2. However, our mining of publically available data from clinical specimens suggest that TDO2 may also need to be targeted in ovarian cancer.