An oestrogen receptor β-selective agonist exerts anti-neoplastic effects in experimental intrahepatic cholangiocarcinoma

Inhibition of lymphoma vascularization and dissemination by estrogen receptor β agonists

“…Inhibition of Granta-519 tumor growth was also seen following treatment with another highly selective ERb agonist, KB099520 (supplemental Figure 2). 5,26,27 Furthermore, the tumorinhibiting effect of DPN was abolished if DPN was coadministered with the ER antagonist ICI 182.780 or impaired when coadministered with estradiol (supplemental Figures 3 and 4a). Note that estradiol is only a weak partial agonist when it comes to inhibition of lymphoma growth in vivo (supplemental Figure 4b), 5 suggesting that the tumor-inhibiting effect indeed was ER-mediated.…”

Targeting estrogen receptor subtypes (ERα and ERβ) with selective ER modulators in ovarian cancer

“…Apart from ovarian cancer, ERb has been implicated in the carcinogenesis of various other malignancies including prostate cancer (Attia & Ederveen 2012), colorectal cancer (Castiglione et al 2008), and cholangiocarcinoma (Marzioni et al 2012). The development of very selective ERb agonists has been very promising in recent years (Mohler et al 2010).…”

Cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA)

“…Although some controversy exists 278,288,290 , simvastatin has been shown to boost the 5-fluorouracil effect in CCA cells by suppressing thymidyl ate synthase expression 292 . Expression of ERs in CCA 93 justifies its sensitivity to tamoxifen 293 and KB9520, which activates apoptosis in experimental CCA 94 . Decreased ER expression might account for a weaker response to this type of drug than CCAs with a high ER expression.…”

“…CCAs are estrogensensitive tumours and the expression of both estrogen receptors (ER-α and ER-β) is generally increased 93 . Although ER-α activation stimulates proliferation of CCA cells 93 , the selective stimulation of the ER-β has antineoplastic effects in vitro and in vivo via induction of apoptosis 94 . Commonly, estrogen-sensitive cancers lose ER-β expression with disease progression; however, the expression of ER-β is maintained in CCA at advanced stages, representing a potential therapeutic target 94 .…”

“…Although ER-α activation stimulates proliferation of CCA cells 93 , the selective stimulation of the ER-β has antineoplastic effects in vitro and in vivo via induction of apoptosis 94 . Commonly, estrogen-sensitive cancers lose ER-β expression with disease progression; however, the expression of ER-β is maintained in CCA at advanced stages, representing a potential therapeutic target 94 . Indeed, administration of the ER antagonist, tamoxifen, or a selective ER-β-selective agonist, KB9520, inhibits CCA growth in vivo 95 .…”