Estrogen and Estrogen Receptor Modulators: Potential Therapeutic Strategies for COVID-19 and Breast Cancer

Abstract

Owing to the ongoing coronavirus disease 2019 (COVID-19) pandemic, we need to pay a particular focus on the impact of coronavirus infection on breast cancer patients. Approximately 70% of breast cancer patients express estrogen receptor (ER), and intervention therapy for ER has been the primary treatment strategy to prevent the development and metastasis of breast cancer. Recent studies have suggested that selective estrogen receptor modulators (SERMs) are a potential therapeutic strategy for COVID-19. With its anti-ER and anti-viral combined functions, SERMs may be an effective treatment for COVID-19 in patients with breast cancer. In this review, we explore the latent effect of SERMs, especially tamoxifen, and the mechanism between ER and virus susceptibility.

Keywords: COVID-19; breast cancer; estrogen receptor; review; selective estrogen receptor modulators.

Figure 1

Scheme of ERα, ERα-46, ERα-36 and ERα-30 structure.

Figure 2

Mechanism of action of endocrine therapies. Ovaries, the adrenal gland, and other organizations produce testosterone that is transformed into estradiol by aromatase. In the presence of circulating estrogen, estrogen receptor (ER)α undergoes conformational changes, form homo- or heterodimers and then migrates to the nucleus, where ERα dimers bind coactivators (CoA) to form a transcriptionally active ERα complex. ERα complex can regulate the transcription and activation of various genes by binding to the estrogen response element (ERE)-encoding gene or interacting with other transcription factors. Aromatase inhibitors block estrogen production by inhibiting androgen conversion to estrogens. Selective estrogen receptor modulators (SERMs) competitively inhibit the binding of estrogen to ERα. SERM-bound ER dimers bind to co-repressors (CoR) inhibiting ER transcriptional activity in breast cancer tissues. Selective estrogen receptor downregulators (SERDs) downregulate the receptor protein expression by inducing ER degradation.