Role of estrogen receptors in cancer: a special emphasis on the therapeutic potential of estrogen receptor β

Estrogen receptors are nuclear receptors that play a major role in both physiology and pathology. Estrogen receptor subtypes are currently divided into three groups: estrogen receptor alpha (ERα), estrogen receptor beta (ERβ), and G protein-coupled estrogen receptor 1 (GPER1 or formerly known as GPR30 or GPRx, a membrane-bound receptor). Overexpression of ERα and GPER1 are known to contribute to cancer, with ERα playing the most important impact. On the other hand, it is commonly acknowledged that ERβ inhibits ERα activity and has anti-cancer properties. As a result, the estrogen receptors ERα and ERβ are the most investigated, with ERα being recognized therapeutically as a therapeutic target for breast cancer. Unlike ERα, which must be blocked, ERβ is a target that has anti-cancer properties when activated. The potential anti-cancer efficacy of ERβ has been demonstrated in several pre-clinical and clinical investigations. In this review, we summarize the potential role of ERβ and ERβ agonists in various cancers.