COVID-19 Molecular Crosstalk with Prostate Cancer: Possible Therapeutic Applications

COVID-19 Molecular Crosstalk with Prostate Cancer: Possible Therapeutic Applications
Fatemeh Akbarian,^1,* Sanam Reza Zadeh,²
1. Genetics Department, Ale-Taha institute of Higher Education
2. Genetics Department, Ale-Taha institute of Higher Education
Introduction: The universal pandemic of coronavirus disease 2019 (COVID-19), termed SARS-CoV-2 by the World Health Organization (WHO), is an illness caused by a new coronavirus.
Methods: While prostate cancer (PCa) is the second most common cancer in men worldwide, the incidence and mortality rate of COVID-19 positive prostate cancer patients are increased to 16.76% and 20%, respectively. The effective factors on the intensity of COVID-19, such as diabetes, alcoholism, hypertension, and active smoking are also known to affect the progression of prostate cancer. This crosstalk is related to potential association among SARS-CoV-2 effect on host epithelial cells and prostate cancer genetic abnormality and molecular signatures, such as AR and TMPRSS2. As the molecular mediators of SARS-CoV-2 infection, antiandrogen- converting enzyme 2 (ACE2) and transmembrane protease, serine 2 (TMPRSS2) genes are co-expressed on ciliated bronchial epithelial cells, type 2 pneumocytes and the epithelial cells of small intestine. The virus spike glycoprotein (S) is primed by TMPRSS2 protease to invade the host cells. TMPRSS2 gene is extremely identified in the male urogenital system organs, including the prostate gland.
Results: Prostate cancer treatments that target SARS-CoV-2 are considered effective when used in blend with other potential repositioned drugs that may be beneficial versus COVID-19. Anti- androgen drugs and TMPRSS2 deterrents used on prostate cancer are suggested to stimulate protective role against SARS- CoV-2 and may perform as regular therapeutic selections for COVID-19 patients. It is hypothesized that the strategy of down- regulating TMPRSS2 by androgen elimination through classical androgen-deprivation drugs (e.g. leuprolide) and oral AR signaling inhibitors (e.g. enzalutamide, apalutamide or darolutamide), that are frequently consumed in prostate cancer treatment, might also be beneficial as a treatment for COVID-19. Although it should be noted that androgen deprivation therapy (ADT) which has been safely used for extensive span, do not afford oncology benefit and can supply to immoderate morbidity or fatality.
Conclusion: Thus, due to this possible molecular crosstalk between SARS- CoV-2 and prostate cancer, it is suggested to examine the possibility of repurposing prostate cancer treatments for COVID-19, alone or in combination with other therapeutics, in order to decrease the serious side effects and increase the specificity and efficacy of treatment.
Keywords: COVID-19; SARS-CoV-2; prostate cancer; androgen deprivation therapy; TMPRSS2