Prostate Cancer Regulator May Be Missing Link for Coronavirus Treatment

December 30, 2020 13:05:51

Scientists now have an encouraging lead on a coronavirus treatment after borrowing a page from prostate cancer. Two proteins — TMPRSS2 and ACE2 — assist the coronavirus in accessing an individual’s body and multiplying within the body’s cells. Arul Chinnaiyan, who is director of the Michigan Center for Translational Pathology, is familiar with the TMPRSS2 protein, seeing as it was his lab that discovered that the protein merges with the ETS gene to cause a majority of the prostate cancers. The researchers at the lab were also aware that the androgen receptor regulated the TMPRSS2 protein.

Earlier this year, Chinnaiyan’s laboratory turned its mind and attention to the coronavirus. The group of researchers utilized the knowledge they already possessed and the resources provided, including a grant from the National Cancer Institute, to find out how the TMPRSS2 protein was modulated in an individual’s lungs.

The researchers discovered that, even in the lungs, the androgen receptor regulated the protein, much like in prostate cancer. They found that a lower expression of both the ACE2 and the TMPRSS2 proteins was observed when the androgen receptor was blocked. In turn, this led to a reduced coronavirus infection in cellular models and in mice used for the study. The study results were reported in the “PNAS” journal.

Chinnaiyan stated that the fact that anti-androgen treatments had already been approved by the FDA was appealing. He explained that this made it easier for researchers to study these drugs as potential coronavirus treatments, because they are already known to be effective in treating prostate cancer.

The researchers also used cell lines that had been contaminated with SARS-CoV-2, the virus that causes the coronavirus, to discover that androgen receptor inhibitors such as apalutamide, enzalutamide and darolutamide impeded the coronavirus infection.

Additionally, they tested drugs that had been developed to degrade or inhibit BET proteins. In doing so, they found that the BET inhibitors slowed infection of the virus and reduced androgen signaling in cell lines that had been contaminated with COVID-19.

The researchers’ findings also gave some explanation regarding the observations that the coronavirus affects more men than women. The scientists observed human lung tissue and discovered that androgen receptors signaling was higher in men than in women. Signaling levels increased significantly in smokers and men who are over the age of 70.

Currently, a number of clinical trials are being conducted that test the use of androgen receptor inhibitors as a treatment for the coronavirus.

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