Researchers have a good lead on treatment for COVID-19 after learning from prostate cancer. The SARS-CoV-2 virus causes Coronavirus Disease (COVID-19), an infectious disease.
The majority of those infected with the virus will have mild to moderate respiratory symptoms and will recover without the need for medical attention. Some, on the other hand, will become extremely unwell and require medical assistance.
Serious sickness is more likely to strike the elderly and those with underlying medical disorders such as cardiovascular disease, diabetes, chronic respiratory disease, or cancer. COVID-19 can make anyone sick and cause them to get very ill or die at any age.
ACE2 and TMPRSS2 are two proteins that assist the coronavirus enter and proliferate within cells. Arul Chinnaiyan, M.D., Ph.D., is familiar with TMPRSS2. TMPRSS2 fusing with the ETS gene caused more than half of all prostate tumors, according to his research. They also recognized that the androgen receptor controlled TMPRSS2.
When cancer research came to an end in the spring, Chinnaiyan’s lab focused on the coronavirus. The researchers used existing information and resources to identify how TMPRSS2 was regulated in the lungs, thanks to a funding from the National Cancer Institute.
This explains why elderly men who are smokers are more vulnerable to COVID-19 infection. High androgen receptor signaling allows the virus to gain entry and replicate more easily. This may explain why the disease is often particularly severe in older men.
Arul Chinnaiyan
They discovered that the androgen receptor regulates TMPRSS2 in the lungs, much as it does in prostate cancer. Blocking the androgen receptor, in particular, resulted in lower expression of TMPRSS2 and ACE2, as well as reduced coronavirus infection in mice and cellular models. The findings were reported in the journal PNAS.
“What’s especially appealing about this is that anti-androgen treatments are already FDA-approved. This opens the door to look at these drugs, which we know work in prostate cancer, as potential COVID-19 treatments,” says Chinnaiyan, director of the Michigan Center for Translational Pathology.
Researchers discovered that inhibitors of the androgen receptor, such as enzalutamide, apalutamide, and darolutamide, suppressed the coronavirus infection in cell lines infected with SARS-CoV-2, the virus that causes COVID-19.
They also looked at a group of medicines that were designed to block or degrade BET proteins. The function of the BET protein is required for androgen signaling, and these medicines are being tested for prostate cancer. The BET inhibitors reduced androgen signaling and prevented viral infection in coronavirus-infected cell lines.
The findings also provide some insight into why men are more affected by COVID-19 than women. In a study of human lung tissue, researchers discovered that men have more androgen receptor signaling than women. Androgen signaling was found to be higher among males over 70 and smokers.
The National Cancer Institute (NCI) is the primary governmental institution in charge of cancer research and education. To improve scientific knowledge and help all people live longer, healthier lives, the National Cancer Institute (NCI) leads, conducts, and funds cancer research across the country.
“This explains why elderly men who are smokers are more vulnerable to COVID-19 infection. High androgen receptor signaling allows the virus to gain entry and replicate more easily. This may explain why the disease is often particularly severe in older men,” Chinnaiyan says.
When cells in the prostate gland begin to grow out of control, prostate cancer develops. The prostate gland is only found in men. It produces some of the fluid found in sperm. Adenocarcinomas account for nearly all prostate cancers. These tumors arise from the cells of the glands (the cells that make the prostate fluid that is added to the semen).
Several clinical trials use androgen receptor inhibitors as a therapy for COVID-19 are now underway, with further trials involving BET inhibitors in the works.
Additional authors: Yuanyuan Qiao, Xiao-Ming Wang, Rahul Mannan, Sethuramasundaram Pitchiaya, Yuping Zhang, Jesse W. Wotring, Lanbo Xiao, Dan R. Robinson, Yi-Mi We, Jean Ching-Yi Tien, Xuhong Cao, Stephanie A. Simko, Ingrid J. Apel, Pushpinder Bawa, Steven Kregel, Sathiya P. Narayanan, Gregory Raskind, Stephanie J. Ellison, Abhijit Parolia, Sylvia Zelenka-Wang, Lisa McMurry, Fengyun Su, Rohit Mehra, Jonathan Z. Sexton
Funding: Prostate Cancer Foundation, National Cancer Institute grants including a COVID-19 supplement to P30-CA046592, P50-CA186786, R35-CA231996, and U01-CA 214170.
