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Pervasive and understudied: The plight of the prostate

Stanford Medicine urologist discusses the future of research regarding prostate enlargement and how he plans to investigate the condition.

Am I the only one who didn't know that virtually all men, after a certain age, experience prostate enlargement? All men!

Now, I'm not a man, so maybe it's my own blissful ignorance, but that statistic shocked me. It surprised me further when James Brooks, MD, a leading urologist at Stanford Medicine, told me that the field of benign urology research, which encompasses prostate enlargement, is wildly understudied -- and underfunded. It's part of the reason, Brooks said, that he's shifted his research focus to understanding why it happens and how to stop it.

Prostate enlargement, or benign prostatic hyperplasia, is a condition in which the prostate, a gland responsible for producing fluid that nourishes and carries sperm, grows and obstructs the urethra. "It's the reason grandpa gets up to go to the bathroom so often at nighttime," said Brooks, Stanford's Keith and Jan Hurlbut Professor of urology.

The condition is not life-threatening, but to call it benign may undersell just how much it impacts a person's quality of life. Prostate enlargement increases frequency of urination and, in more severe cases, blocks urination, which can cause kidney damage.

I spoke with Brooks about his approach to understanding what causes prostate enlargement -- one of the condition's great mysteries -- and how he plans to harness a new grant from the National Institutes of Health to help decipher its roots and how to better treat it.

You've said that nearly all men experience benign prostatic hyperplasia. Why is it so understudied and underfunded?

I think there are a few reasons. First -- the questions are kind of difficult. For instance, what is benign prostatic hyperplasia? We know the prostate starts growing as men age, particularly in a middle segment of the gland known as the transition zone. That phenomenon is rare, and it only happens in benign prostatic hyperplasia and during lactation when women breastfeed. The researcher who first observed this thought it might be the result of a sort of embryonic reawakening of tissues, but we really don't know what genetic or molecular pathways are involved in that growth.

Also, there's really no advocacy for benign prostatic hyperplasia. There is a ton of advocacy from patients and government entities for finding treatments and cures for diseases like prostate, lung and kidney cancer, which all kill people. That means more funding.

So the research is difficult, the funding is scanty and the endpoints -- the things you measure to determine patient progress -- are subjective. One patient might wake up three or four times a night to urinate, but he isn't bothered by it. Another might wake up once and he's driven crazy. That makes research and treatment progress harder to track.

What does this new grant help you to explore?

This grant, called an O'Brien Center, is pretty unique. We are one of three centers for benign urology research in the country that the NIH views as a hub and training center for growing benign urology research. Our big question is, how do you figure out why these tissues take off and grow like this? It's not trivial. I worked in cancer most of my career and for cancer there's a decent blueprint: a gene gets mutated, which that leads to unrestricted growth. There are all kinds of alterations we can look for, and we have specific tools to do so. There's nothing like that in benign prostatic hyperplasia.

Where do you get a toehold into understanding why these tissues have started growing like this? That's what we're working toward solving and we've investigated specific genes and their roles in prostate enlargement. This grant will help us continue that research.

What prompted you to pivot from your focus on cancer and surgery to specializing in benign prostatic hyperplasia?

Old age. No, I'm kidding. I'm tantalized by the idea that this is an under-researched area. I've spent a lot of time in cancer research and have made some contributions over the years. But at this point in my career, I would like to take a swing at something else and see if I can make some contributions there. I've been thinking about this problem with my colleagues on the NIH grant, Robert West, MD, PhD, and John Pollock, MD, PhD, for 10 years now. We realized that, if we put our scientific energies towards this question, it could be the place where we make our biggest impact.

Also, there is no happier man on the planet than a man who's had an operation and suddenly can urinate well again. It's kind of one of those little miracles that happens every day. Fixing this problem for patients and making them that happy was really appealing to me.

What do you hope comes of your research?

Treatment options for benign prostatic hyperplasia are kind of limited. Urologists are responsible for benign urology and urology, as a field, was spun out of general surgery departments. So it makes sense that many urology treatment options are surgical, as is the case with benign prostatic hyperplasia.

There are also some drugs that relax the smooth muscle component of the prostate and the lower part of the bladder, which opens the urethra to some extent, helping men have a better urinary stream. There are other drugs that can shrink the prostate by blocking the metabolism of testosterone. Those drugs work for some patients, to varying degrees, but sometimes they don't work at all.

The field has been more focused on fixing the problem than understanding the causes. We're using something called single cell RNA sequencing to investigate the cause and identify the various cell types in the prostate. We are also characterizing the locations of the cell types and chemicals or proteins they're making, to understand how cells in the prostate talk to each other to turn on growth that causes prostate enlargement.

Photo by By Syda Productions

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