Abstract
The estrogen receptor (ER) has functionality in selected ovarian cancer subtypes and represents a potential target for therapy. The majority (>80%) of high grade serous, low grade serous and endometrioid carcinomas and many granulosa cell tumors express ER-alpha (ERα), and these tumor types have demonstrated responses to endocrine therapy (tamoxifen and aromatase inhibitors) in multiple clinical studies. Biomarkers of responses to these drugs are actively being sought to help identify responsive cancers. Evidence for both pro-proliferative and pro-migratory roles for ERα has been obtained in model systems. ER-beta (ERβ) is generally considered to have a tumor suppressor role in ovarian cancer cells, being associated with the repression of cell growth and invasion. The differential expression of the specific ERβ isoforms may determine functionality within ovarian cancer cells. The more recently identified G protein-coupled receptor (GPER1; GPR30) has been shown to mediate both tumor-suppressive and tumor-promoting action in ovarian cancer cells, suggesting a more complex role. This review will summarize recent findings in this field.
Highlights
Ovarian cancer continues to be the most lethal gynecological cancer in the Western world, largely due to its frequently late diagnosis; approximately 300,000 new cases and 185,000 deaths are reported worldwide each year [1]
Evaluation of the roles of the estrogen receptor (ER) subtypes in Granulosa cell tumors (GCTs) has suggested that ERβ expression may be of particular significance in these tumors
While the above studies support a role for higher levels of ERα expression mediating the effects of anti-estrogens, the roles of ERβ and GPER1 remain relatively unexplored with respect to the response to tamoxifen and other anti-estrogens in this disease setting
Summary
Ovarian cancer continues to be the most lethal gynecological cancer in the Western world, largely due to its frequently late diagnosis; approximately 300,000 new cases and 185,000 deaths are reported worldwide each year [1]. 66 kDathat receptor truncated isoforms, ERα46signaling and ERα36, have been receptor binds(ERα66), estrogen two and other activates multiple downstream pathways These described [10], and the former (but not the latter) has been observed within ovarian cancer cells calcium [11]. It is apparent that several of the major forms of ovarian cancer—namely HGSOC, LGSOC, endometrioid ovarian carcinoma and adult-type GCTs—show greater sensitivity to estrogen and can respond to strategies that either inhibit the production of estrogen (i.e., aromatase inhibitors) or that directly compete with its action at estrogen receptors (i.e., anti-estrogens such as tamoxifen or fulvestrant), which may have therapeutic value in selected groups of ovarian cancer patients. This review will focus on estrogen signaling and its impact on the risk, incidence, development, progression and therapy of differing forms of ovarian cancer with an emphasis on the responsive ovarian cancer subgroups
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