To the Editor, We are writing to highlight the importance of considering common themes that link prostate cancer and SARS-CoV-2, and which might provide worthwhile areas for future research. Prostate cancer is the most common type of cancer among men in 112 countries (Sung et al. 2021). In recent years, treatments and preventive clinical approaches have focused on androgen receptors (AR) and their hormones. More recently, studies have suggested that estrogens and estrogen receptors are potential factors in the biology and tumorigenesis of prostate cancer that need to be better understood (Bonkhoff and Berges 2009). In this context, the transmembrane protease serine 2 (TMPRSS2) is a key component as it plays a role in both hormone pathways. Recently, it has become a focus of attention due to its participation in infection in SARS-CoV-2. TMPRSS2 is a type II transmembrane serine protease, which is typically expressed on the cell surface of the prostate epithelium. This expression is normally higher in the prostate cells than in any other tissue of the human body and is even greater in high-grade and aggressive prostate tumors (Lucas et al. 2014). The TMPRSS2 pathway is regulated by AR signaling via transactivation, as demonstrated by Lucas et al. (2014), and is a pivotal upregulated factor in aggressive primary localized prostate tumors and metastatic prostate tumors. The androgenic pathways play important roles in prostate tumorigenesis and can be supported by the androgen deprivation therapies currently used in the treatment of prostate cancer. However, they are not the only routes through which cancer progression can proceed. The existence of castration-resistant tumors in men and the evidence of estrogen signaling in prostate tumors reinforces the existence of multiple molecular and hormonal pathways in prostate cancer. Both estrogen receptor alpha (ER-α) and estrogen receptor beta (ER-β) are expressed in the human prostate in stromal and luminal cells, respectively, and 17β-estradiol binds to them (Bonkhoff and Berges 2009). Prostate tumors frequently exhibit gene rearrangements with the most recurrent being the gene fusion of TMPRSS2 to erythroblast transformation specific coding regions, including ERG (ETS (erythroblast transformation specific) related gene) and ETV (ETS variant transcription factor) (Tomlins et al. 2005). An analysis conducted by Xu et al. (2018) found that TMPRSS2:ERG gene fusion is implicated in the upregulation of levels of ER-α and ERG mRNAs in prostate tumors, and their higher expression was particularly correlated to metastatic prostate cancer. According to the authors, the use of ER-α antagonists and ER-β agonists might inhibit the TMPRSS2:ERG expression (Xu et al. 2018). This potential approach needs further study. A new coronavirus was discovered in China in 2019 – severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and has since spread around the globe, causing a pandemic, and leading to many deaths and comorbidities. The infection of human cells by this novel virus depends primarily on the binding of a viral spike (S) protein to the cell receptors angiotensin-converting enzyme 2 and TMPRSS2 (Hoffmann et al. 2020). Given that TMPRSS2 is involved in both pathophysiological processes – prostate cancer progress and SARS-CoV-2 cell entry, we highlight its importance in future epidemiological and clinical studies, particularly in men infected by the virus. Some possible associations and points of attention are as follows: (1) serine protease inhibitors and TMPRSS2 inhibitors developed as treatments to block the SARS-CoV-2 infection may be of importance to prostate tumors therapies; (2) as TMPRSS2 signaling is involved in the androgen and estrogen pathways, both of which are involved in the physiology of the normal prostate and in prostate cancer progression, the novel coronavirus may have impacts on this gland tissue and the surrounding tissues. Further longitudinal designed studies may help to analyze these possible effects; (3) prostate cancer is usually diagnosed in men who are over 50 years and fatal cases of SARS-CoV-2 infection are also concentrated in older ages (Dowd et al. 2020). Many cancer treatments must follow extremely specific time periods to achieve suitable results, making the simultaneous management of both disease therapies a real challenge and (4) as SARS-CoV-2 coronavirus already binds to the TMPRSS2 receptor, present in prostate tumor cells, future studies should evaluate its possible use as an oncolytic virus for prostate cancer immunotherapy. We are not planning to discard other possibilities in regards to those overlaps between the two conditions presented here. Nevertheless, considering the current perspectives, these outlines listed above include some of the most relevant possibilities for future studies. Acknowledgements Our studies are supported by the Associação Fundo de Incentivo à Pesquisa (AFIP), São Paulo, Brazil. M.L.A. and S.T. are recipients of Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) fellowships. No sponsorship was received for the publication of this manuscript. All named authors take responsibility for the integrity of the work as a whole and have given their approval for this version to be published. A.S.P. was responsible for writing the first draft of the manuscript, reference organization and manuscript revision. M.L.A. and S.T. were responsible for the manuscript design and critical revision for important intellectual content. Conflicts of interest There are no conflicts of interest.