Abstract S01-03: A prediction of prostate cancer deaths spiking by SARS-CoV-2 infection
Authors: Bera Alakesh , Russ Eric , Chatterjee Digonto , Karaian John , Subramanian Madhan , Chatterjee Sreejato , Radhakrishnan Surya , Eklund Michael , Pollard Harvey , Srivastava Meera 
Published: December 2020

Abstract
COVID-19 is a global issue, with over 6.25 million cases in 213 countries and territories on June 1, 2020. Although this virus infects all groups, data indicate that the risk for severe disease and death is much higher in older men, which coincides with the same group of patients at risk for prostate cancer. A recent Italian study investigated the prevalence and severity of COVID-19 in men with prostate cancer. This study indicated that of a total of 4,532 men with COVID-19, from the Veneto region of Italy, 9.5% (n=430) had cancer and out of those around 30% (n=118) had prostate cancer. Data also indicated that male cancer patients had a 1.8-fold increased risk of COVID-19 infection and developed a more severe disease. Interestingly, they observed that the prostate cancer patients (n=4) treated with androgen-deprivation therapy (ADT) were less likely to develop COVID-19, and in those who were infected, the disease was less severe. In this current study, we focused on determining the genetic basis of the higher COVID-19 prevalence and severity in male patients and particularly for prostate cancer patients. Researchers found two genes that are essential for severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2). ACE2 is a SARS-CoV-2 receptor, whereas the serine protease, TMPRSS2, primes the virus for cell entry through cleavage of the viral spike protein (S). The expression of TMPRSS2 is significantly high in normal prostate tissue and is regulated in large part by an androgen response element in the promoter region. Therefore, we decided to investigate the status of these two genes in various tumors from The Cancer Genome Atlas (TCGA) database using the cBioportal platform. We analyzed over 46,000 tumor samples from 176 studies and found that aggressive metastatic prostate cancer, including neuroendocrine prostate cancer (NEPC), has significantly higher amplification (copy number alteration) of the ACE2 and TMPRSS2 genes compared to other cancers. Next, we focused on drugs that could simultaneously target ACE2 or TMPRSS2 and oncogenic pathways and would be beneficial for prostate cancer patients infected with SARS-CoV-2. Although several inhibitors are validated in literature for both ACE2 and TMPRSS2, very limited studies were performed to see the effect on cancer cells. Therefore, we analyzed a cytotoxic effect database of over 130,000 drugs on NCI-60 cell lines with COMPARE algorithm and found two relevant compounds, NSC-148958 (FT-701) and NSC-280594 (triciribine phosphate), which target ACE2 and TMPRSS2, respectively. Computational data are currently validating different prostate cancer cell-lines and their response to these drugs. In summary, our findings provide the premise that men who are at risk for or diagnosed with prostate cancer may be more susceptible to severe infection and death in response to SARS-CoV-2 due to the high expression of ACE2 and TMPRSS2, and triciribine phosphate and FT-701 could be a therapeutic intervention to target co-occurrence of COVID-19 and prostate cancer.
Citation Format: Alakesh Bera, Eric Russ, Digonto Chatterjee, John Karaian, Madhan Subramanian, Sreejato Chatterjee, Surya Radhakrishnan, Michael Eklund, Harvey Pollard, Meera Srivastava. A prediction of prostate cancer deaths spiking by SARS-CoV-2 infection [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr S01-03.