Abstract 709: Estrogen and androgen receptor inhibitors: Unexpected allies in the fight against COVID-19
Authors: Bravaccini Sara , Fonzi Eugenio , Tebaldi Michela , Angeli Davide , Martinelli Giovanni , Nicolini Fabio , Parrella Paola , Mazza Massimiliano 
Published: July 2021

Abstract
IntroductionGiven the COVID-19 coronavirus emergency, a special focus is needed on the impact of this rapidly spreading viral infection on cancer patients. 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. Androgen receptor (AR) signaling in the TMPRSS2 regulation is emerging as an important determinant of SARS-CoV-2 susceptibility.
Materials and MethodsIn our study, we analyzed AR and TMPRSS2 expression in 17352 normal and 9556 cancer tissues from public repositories and stratified data according to sex and age. Gene expression data were retrieved from TCGA and Genotype-Tissue Expression (GTEx) portal. Differences in gene expression were tested with Mann-Whitney U-test.
ResultsThe emerging picture is that some patient groups may be particularly susceptible to SARS-CoV-2 infection and may benefit from anti-androgen or anti-estrogen based therapies. Indeed, while young individuals showed a coherent reduction of AR expression in tumors as compared to healthy tissues regardless of gender, elderly females showed increased AR levels in tumors compared to normal tissues. Coherently with AR overexpression, we also observed a significant increase in TMPRSS2 gene expression in tumors from elderly females with respect to age-matched normal tissues. These results highlight that cancers of elderly females have typically higher expression of AR and of TMPRSS2 identifying a population of cancer patients that may be particularly susceptible to COVID-19 infection.
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.
ConclusionsWe 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.
Citation Format: Sara Bravaccini, Eugenio Fonzi, Michela Tebaldi, Davide Angeli, Giovanni Martinelli, Fabio Nicolini, Paola Parrella, Massimiliano Mazza. Estrogen and androgen receptor inhibitors: Unexpected allies in the fight against COVID-19 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 709.