Repurposing Bazedoxifene for Cancer Therapeutics: It is Much more than a SERM
Asian Oncology Research Journal · pp. 197–212 · Published 11 Dec 2020
Abstract
Bazedoxifene (BDF) is a selective estrogen receptor modulator (SERM) that has been approved by the FDA for the treatment of post-menopausal osteoporosis in association with conjugated estrogens. BDF shares many of the pharmacological effects of tamoxifen with the advantage of not being an ER agonist in uterus and decreasing the risk for endometrial carcinoma induced by tamoxifen. Interestingly, BDF has shown anti-tumoral actions in tissues and tumors that are hormone-independent. This means that BDF is not only a SERM. The better known of these mechanisms are • Inhibition of the IL6-IL6R-GP130-STAT 3 axis (IL6: interleukin 6; IL6R: interleukin 6 receptor; GP130: glycoprotein 130; STAT3: Signal Transducers and Activators of Transcription-3. • Modulation of the Hippo-YAP pathway. • Inhibition of AOX1 (aldehyde oxidase 1) The first two are neatly anti-tumoral. The third one is sort of controversial. This review is focused on the non-hormonal anti-tumor mechanisms of BDF. Its repurposing for the treatment of malignancies, other than breast cancer, is analyzed.
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