The Role of Estrogen in Ovarian Cancer and the Pathways by Which Estrogen Acts

Ovarian cancer remains a prevalent and deadly cancer in females. While anti-estrogen therapies have been useful in the treatment of other cancer types, their effectiveness in the treatment of ovarian cancers remains limited due to the limited understanding of estrogen's effects on carcinogenesis and growth promotion in these tissues. This paper aims to summarize the role estrogen plays in ovarian cancer tumorigenesis and its potential value in targeted therapeutics. Estrogen's effects are secondary to interactions with estrogen receptor (ER) α, ER β, and the G protein coupled receptor, GPR30. Genomic signaling of ER-α has been shown to be primarily carcinogenic, while that of ER-β has been shown to be a negative regulator of carcinogenesis. Additionally, ER-α has been found to have carcinogenic effects through non-genomic signaling of the p53, MAPK, EGFR/Her2, PI3K, and IGF/IGFR pathways. GPR30's effects have been found to be more variable and specific to tumor classification. For example, GPR30 is primarily carcinogenic in ovarian epithelial tumor types but appears to have protective effects when highly expressed in granulosa cell tumors. While the above generalizations can be made, a better understanding of estrogen's effects on molecular signaling pathways will potentially allow for development of more effective targeted therapies against ovarian cancer.