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. 2021 Jan-Dec:30:963689721991477.
doi: 10.1177/0963689721991477.

Estrogen and Androgen Receptor Inhibitors: Unexpected Allies in the Fight Against COVID-19

Sara Bravaccini  1 , Eugenio Fonzi  2 , Michela Tebaldi  2 , Davide Angeli  2 , Giovanni Martinelli  1 , Fabio Nicolini  3 , Paola Parrella  4 , Massimiliano Mazza  3
Affiliations

Estrogen and Androgen Receptor Inhibitors: Unexpected Allies in the Fight Against COVID-19

Sara Bravaccini et al. Cell Transplant. 2021 Jan-Dec.

Abstract

Translational relevance: No prophylactic treatments for COVID-19 have been clearly proven and found. In this pandemic context, cancer patients constitute a particularly fragile population that would benefit the best from such treatments, a present unmet need. TMPRSS2 is essential for COVID-19 replication cycle and it is under androgen control. Estrogen and androgen receptor dependent cues converge on TMPRSS2 regulation through different mechanisms of action that can be blocked by the use of hormonal therapies. We believe that there is enough body of evidence to foresee a prophylactic use of hormonal therapies against COVID-19 and this hypothesis can be easily tested on cohorts of breast and prostate cancer patients who follow those regimens. In case of pandemic, if the protective effect of hormonal therapies will be proven on cancer patients, the use of specific hormonal therapies could be extended to other oncological groups and to healthy individuals to decrease the overall risk of infection by SARS-CoV-2.

Given the COVID-19 coronavirus emergency, a special focus is needed on the impact of this rapidly spreading viral infection on cancer patients. Androgen receptor (AR) signaling in the transmembrane protease serine 2 (TMPRSS2) regulation is emerging as an important determinant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) susceptibility. In our study, we analyzed AR and TMPRSS2 expression in 17,352 normal and 9,556 cancer tissues from public repositories and stratified data according to sex and age. The emerging picture is that some patient groups may be particularly susceptible to SARS-CoV-2 infection and may benefit from antiandrogen- or tamoxifen-based therapies. These findings are relevant to choose proper treatments in order to protect cancer patients from concomitant SARS-CoV-2 contagion and related symptoms and put forward the idea that hormonal therapies could be used as prophylactic agents against COVID-19.

Keywords: SARS-CoV-2; TMPRSS2; breast and prostate cancer patients; hormonal therapy; tamoxifen.

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Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: GM has competing interests with Novartis, BMS, Roche, Pfizer, ARIAD, and MSD not related to this manuscript. All the other authors have no conflicts of interest to declare.

Figures

Figure 1.
Figure 1.
Role of AR and hormonal therapies in TMPRSS2 expression. Comparison of AR gene expression between healthy donor tissues and TCGA cancers according to sex and age categories is shown (A); comparison of AR (B) and TMPRSS2 (C) expression between healthy donor tissues and TCGA cancers in elderly females; and (D) schematic representation of hormonal therapies in prostate and breast tumors and their effects on AR function and TMPRSS2 expression. Healthy donor tissues are displayed as green boxplots; cancers from TCGA data are displayed as red boxplots; *FDR < 0.05, **FDR < 0.01, ***FDR < 0.001. AR: androgen receptor; TMPRSS2: transmembrane protease serine 2; FDR: False Discovery Rate.
See this image and copyright information in PMC

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