In a new study, researchers found that drugs that target the androgen receptor – successful in controlling prostate cancer – may also work against the coronavirus.
By taking a lesson from prostate cancer, they now have a promising lead on treatment for COVID-19.
The research was conducted by a team at the University of Michigan.
Two proteins, ACE2 and TMPRSS2, help the coronavirus gain entry and replicate within cells.
TMPRSS2 fuses with the ETS gene to drive more than half of all prostate cancers. It can be regulated by the androgen receptor.
In the study, the team examined how TMPRSS2 was regulated in the lungs.
They found that, just like in prostate cancer, TMPRSS2 is regulated by the androgen receptor in the lungs.
And notably, blocking the androgen receptor led to lower expression of TMPRSS2 as well as ACE2, which led to decreased coronavirus infection in mice and cellular models.
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 researchers know work in prostate cancer, as potential COVID-19 treatments.
Using cell lines infected with SARS-CoV-2, the virus that causes COVID-19, researchers found that inhibitors of the androgen receptor, including enzalutamide, apalutamide and darolutamide, reduced the COVID-19 infection.
They also tested a class of drugs designed to inhibit or degrade BET proteins. BET protein activity is essential for androgen signaling and these drugs are being looked at for prostate cancer.
In cell lines infected with coronavirus, the BET inhibitors decreased androgen signaling and inhibited viral infection.
The findings also provide some explanation for observations that COVID-19 affects men more than women.
The team looked at human lung tissue and found higher androgen receptor signaling in men than women. They also found androgen signaling was highest in men over 70 and in smokers.
The team says 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.
Several clinical trials are underway testing androgen receptor inhibitors as a treatment for COVID-19, and additional trials are being developed to look at BET inhibitors.
One author of the study is Arul Chinnaiyan, M.D., Ph.D.
The study is published in PNAS.
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