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雌激素和雄激素受体抑制剂:抗击 COVID-19 的意外盟友。

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

机构信息

Bioscience Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, FC, Italy.

Unit of Biostatistics and Clinical Trials, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, FC, Italy.

出版信息

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

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.

UNLABELLED

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.

摘要

翻译

在没有明确证实和发现 COVID-19 预防性治疗方法的情况下,癌症患者在这种大流行背景下构成了一个特别脆弱的群体,他们最需要这些治疗方法,而这一需求目前尚未得到满足。TMPRSS2 对 COVID-19 复制周期至关重要,并且受雄激素控制。雌激素和雄激素受体依赖性信号通过不同的作用机制汇聚到 TMPRSS2 调节上,这些机制可以通过使用激素疗法来阻断。我们认为有足够的证据可以预见激素疗法在预防 COVID-19 方面的应用,并且可以很容易地在接受这些治疗方案的乳腺癌和前列腺癌患者队列中对这一假说进行测试。如果在大流行期间,激素疗法对癌症患者的保护作用得到证实,那么特定的激素疗法可以扩展到其他肿瘤学群体和健康个体,以降低感染 SARS-CoV-2 的总体风险。

未加标签的部分

鉴于 COVID-19 冠状病毒的紧急情况,需要特别关注这种快速传播的病毒感染对癌症患者的影响。雄激素受体(AR)信号在跨膜丝氨酸蛋白酶 2(TMPRSS2)调节中作为严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)易感性的重要决定因素正在出现。在我们的研究中,我们分析了来自公共存储库的 17352 份正常组织和 9556 份癌症组织中的 AR 和 TMPRSS2 表达,并根据性别和年龄对数据进行了分层。出现的情况是,一些患者群体可能特别容易感染 SARS-CoV-2,并且可能受益于抗雄激素或他莫昔芬为基础的治疗。这些发现对于选择适当的治疗方法以保护癌症患者免受 SARS-CoV-2 感染和相关症状具有重要意义,并提出了激素疗法可作为 COVID-19 预防性药物的想法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33cf/7863556/4201dff6ab43/10.1177_0963689721991477-fig1.jpg

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