Update on the therapeutic significance of estrogen receptor beta in malignant gliomas

Malignant glioma is the most fatal of the astrocytic lineage tumors despite therapeutic advances. Men have a higher glioma incidence than women, indicating that estrogen level differences between men and women may influence glioma pathogenesis. However, the mechanism underlying the anticancer effects of estrogen has not been fully clarified and is complicated by the presence of several distinct estrogen receptor types and the identification of a growing number of estrogen receptor splice variants. Specifically, it is generally accepted that estrogen receptor alpha (ERα) functions as a tumor promoter, while estrogen receptor beta (ERβ) functions as a tumor suppressor, and the role and therapeutic significance of ERβ signaling in gliomas remains elusive. Thus, a deeper analysis of ERβ could elucidate the role of estrogens in gender-related cancer incidence. ERβ has been found to be involved in complex interactions with malignant gliomas. In addition, the prognostic value of ERβ expression in glioma patients should not be ignored when considering translating experimental findings to clinical practice. More importantly, several potential drugs consisting of selective ERβ agonists have exhibited anti-glioma activities and could further extend the therapeutic potential of ERβ-selective agonists. Here, we review the literature to clarify the anti-glioma effect of ERβ. To clarify ERβ-mediated treatment effects in malignant gliomas, this review focuses on the potential mechanisms mediated by ERβ in the intracellular signaling events in glioma cells, the prognostic value of ERβ expression in glioma patients, and various ERβ agonists that could be potential drugs with anti-glioma activities.