The susceptibility to male bladder cancer could be exploited to develop new therapeutic strategies

A variant of protein that is common in malignant bladder tumor cells may serve as a new way to treat bladder cancer. A multi-institution study conducted by researchers at the UC Davis Comprehensive Cancer Center found that targeting androgen receptors – a type of protein essential for testosterone to function – can destroy cancer cells.

The study, published in the April 28, 2021 issue of Cancer Letters, is important because it showed, for the first time, that a newly identified form of the protein is commonly expressed in bladder tumors and that depletion of that protein led to cell death .

Research has focused on androgens, hormones essential to male sexual development and the growth of the prostate. One type of androgen is testosterone, a hormone that stimulates the development of male sexual characteristics.

Androgen receptors are cellular proteins that are found in the tissues of several organs. These receptors allow the hormones to trigger certain reactions in the body. Androgen hormones bind to the receptors and trigger the expression of ribonucleic acids, which convert information stored in the DNA into proteins.

Prostate cancer treatments include androgen deprivation therapy, which is designed to block androgen receptors from binding to androgens and prevent the growth of malignant cells. Could bladder cancer be treated the same way?

“There is evidence that reducing androgen receptors degrades tumor cells – including those in the bladder,” said Maria Mudryj, lead author on the study and vice chair of education and outreach for the Department of Microbiology and Medicine at UC Davis School of Medicine Immunology.

AR proteins could be key to understanding bladder cancer in men.

Previous studies in patients with bladder cancer showed that androgen receptors were more common in tumor tissue than in normal tissue and in bladder tumors in men than in women. “

Maria Mudryj, lead author of the study

The results correlated with a study in men who had bladder cancer and were treated with drugs called 5α-reductase inhibitors, a class of drugs that have anti-androgenic effects. Fewer men who had this treatment died, suggesting that the AR suppression strategy might be effective for some patients.

However, the researchers don’t yet know whether testing patients for the presence of the AR variants could be used to determine which patients would benefit from certain treatments. Additional studies are required.

“Further research could reveal weaknesses that could be exploited to develop new therapeutic strategies for an effective treatment of malignant bladder diseases,” said Mudryj.

Source:

University of California – Davis Health

Journal reference:

Katleba, K. et al. (2021) Depletion of the low molecular weight isoform of the androgen receptor decreases the viability of bladder tumor cells and induces apoptosis. Cancer letters. doi.org/10.1016/j.canlet.2021.01.029.

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