Bipolar Androgen Therapy

Alwayshope,

That looks an interesting alternative for those of us going Hormone resistant.  
Best wishes,  David

I have found a more comprehensive article for anyone interested.

https://academic.oup.com/oncolo/article/28/6/465/7110907

Thank you for this link AH. It is fascinating how you can confuse the enemy is such a simple way!

Best wishes

Dafna

PS we now both have Covid but my husband still active with mild symptoms

Hope you are not suffering too much with COVID. Take care. We are off for our vaccinations tomorrow, the problem is that our nearest vaccination centre is an hours drive away - not ideal but one of the things we have to put up with for living in a quiet area.

I have been keeping an eye on this technique and have been reading in 'nature' 3.9.2024 that they now think that they have uncovered the mechanisms involved which is good news for men in trying to prevent hormone resistance. I will post the link if anyone is interested but it is very technical.

This is an easier to understand summary.

A treatment paradox has recently come to light in prostate cancer: Blocking testosterone production halts tumor growth in early disease, while elevating the hormone can delay disease progression in patients whose disease has advanced.

The inability to understand how different levels of the same hormone can drive different effects in prostate tumors has been an impediment to the development of new therapeutics that exploit this biology.

Now, a Duke Cancer Institute-led study, performed in the laboratory of Donald McDonnell, Ph.D. and appearing this week in Nature Communications, provides the needed answers to this puzzle.

The researchers found that prostate cancer cells are hardwired with a system that allows them to proliferate when the levels of testosterone are very low. But when hormone levels are elevated to resemble those present in the normal prostate, the cancer cells differentiate. 

For decades, the goal of endocrine therapy in prostate cancer has been to achieve absolute inhibition of androgen receptor function, the protein that senses testosterone levels."

Rachid Safi, Ph.D., lead investigator, research assistant professor in the Department of Pharmacology and Cancer Biology, at Duke University School of Medicine

"It's been a highly effective strategy, leading to substantial improvements in overall survival," he said. "Unfortunately, most patients with advanced, metastatic disease who are treated with drugs to inhibit androgen signaling will progress to an aggressive form of the disease for which there are limited therapeutic options."

Using a combination of genetic, biochemical, and chemical approaches, the research team defined the mechanisms that enable prostate cancer cells to recognize and respond differently to varying levels of testosterone, the most common androgenic hormone.

It turned out to be rather simple. When androgen levels are low, the androgen receptor is encouraged to "go solo" in the cell. In doing so, it activates the pathways that cause cancer cells to grow and spread. However, as androgens rise, the androgen receptors are forced to "hang out as a couple," creating a form of the receptor that halts tumor growth.

"Nature has designed a system where low doses of hormones stimulate cancer cell proliferation and high doses cause differentiation and suppress growth, enabling the same hormone to perform diverse functions," McDonnell said.

In recent years, clinicians have begun treating patients with late-stage, therapy resistant prostate cancers using a monthly, high-dose injection of testosterone in a technique called bi-polar androgen therapy, or BAT. The inability to understand how this intervention works has hindered its widespread adoption as a mainstream therapeutic approach for prostate cancer patients.

"Our study describes how BAT and like approaches work and could help physicians select patients who are most likely to respond to this intervention," McDonnell said. "We have already developed new drugs that exploit this new mechanism and are bringing these to the clinic for evaluation as prostate cancer therapeutics."

In addition to McDonnell and Safi, study authors include Suzanne E. Wardell, Paige Watkinson, Xiaodi Qin, Marissa Lee, Sunghee Park, Taylor Krebs, Emma L. Dolan, Adam Blattler, Toshiya Tsuji, Surendra Nayak, Marwa Khater, Celia Fontanillo, Madeline A. Newlin, Megan L. Kirkland, Yingtian Xie, Henry Long, Emma Fink, Sean W. Fanning, Scott Runyon, Myles Brown, Shuichan Xu, Kouros Owzar, and John D. Norris.

The study received funding support from the National Cancer Institute (R01-CA271168, P30CA014236) and the North Carolina Biotechnology Center.

Source:

Duke University Medical Center

Journal reference:

Safi, R., et al. (2024). Androgen receptor monomers and dimers regulate opposing biological processes in prostate cancer cells. Nature Communications. doi.org/10.1038/s41467-024-52032-y.

Good Afternoon Alwayshope 

You know me, not too technical, but am I right? ( I am in apprentice nerd mode ) It's a trial of a treatment for people with advanced Prostate cancer who's hormone treatment is not working.

You feed the cancer cells some extra testosterone, the cancer cells come out to play and you hit them with the new stronger ADT - and you do it over and over again with the odd break, and boom the cancer cells which have gone "walkabout" are dead.

(oh - I am well thank you I know it's Saturday at 4.00pm but my team are on the telly today - kick off 5.30 and it's a long way away, so no I haven't travelled).

Thanks for the update.

Best wishes - Brian.

Well done apprentice nerd. It sounds a simple cheap solution. It's having to change the mind set that low testosterone is good, high testosterone is bad. There has been work done to see whether testosterone supplementation increases the risk of prostate cancer in both the pre diagnosis and post treatment scenarios and the answer seems to be no. They are also looking to trial the strategy earlier on in treatment for men with advanced prostate cancer.

I take it you will be putting your feet up with a bevvy this evening. Enjoy.

My Oncologist rather dismissed this as an option, I guess it needs to be approved by Nice before it will be included in mainstream treatment. Definitely one to watch I think. David

Alwayshope said:

I take it you will be putting your feet up with a bevvy this evening. Enjoy.

Spot on