Therapy sensitivity in prostate cancer halted by protein regulating circadian rhythm.
Hormone treatment is successful at controlling metastatic prostate cancer, but the tumor cells eventually develop resistance to it. An unexpected potential solution has now emerged in medicines that are not designed to fight cancer, but rather to target proteins that regulate a cell’s circadian rhythm.
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“The circadian rhythm in prostate tumor cells is no longer functional, and the proteins have taken on an entirely new role. This new escape route of the tumor cell has our full attention now, and follow-up research will show whether inhibition of this process can improve prostate cancer treatment.”
Sleep continues to show up as a key component in all aspects of our health. In this case, the researchers have discovered that a class of cellular proteins that in normal cells regulates the circadian cycle is hijacked to protect PCa cells from hormone-based treatments. This eventually drives "tumors towards a neuroendocrine-like disease state". The research will now look for ways to reprogram the circadian clock of PCa cells so that they will continue to respond to ADT.
And while this would not do much to improve the cumulative effects of long-term ADT to your overall health and QOL, it would extend the effectiveness of current hormone treatments and PCa patient's lifespans, esp. for those in danger of becoming CR.)
Here is the link to the SciTechDaily article:
Prostate Cancer Hijacks Tumor Cells’ Circadian Rhythm To Evade Hormone Therapy, Netherlands Cancer Institute, June 27, 2022
And one to the Cancer Discovery abstract (full paper is behind the paywall):
Drug-induced epigenomic plasticity reprograms circadian rhythm regulation to drive prostate cancer towards androgen-independence, Research Article| June 27 2022
Thanks for posting this information. There are several drugs that effect circadian rhythm and melatonin is one of them. I am aware of several classes--benzodiazepines, nonbenzodiazepine hypnotics, and Orexin receptor antagonists. We are aware of studies showing prolonged survival for those taking melatonin. I do wonder if the Orexin receptor antagonists might also have some value in slowing PCa progression-see below:
Sounds like Dangerous Dave is going to put on his fisherman hat (minus the 'np' portion) and head for the nearest river, lake, or pond in a couple of weeks. Be sure to choose a spot with a lot of shade.
As for melatonin, I've been on an escalating dosage over the last 4 or so years, up to my current 30 mg per night. Strangely enough, I had wickedly vivid dreams on the lower dosages, like 3 to 5 mg, but once I increased it to 10 mg and above, I got back to my "normal" dream pattern. It works on multiple pathways to defeat cancer metabolism, so a good supplement for PCa patients to consider.
I'm not at all familiar with your Orexin receptor, but will put it on my long list of things related to our common disease to see what I can find.
Good to hear that you have finally made your decision about your unsatisfactory work situation. Life is way too short to do something for 40 hours a week that is not rewarding to you. Also sounds like you have plenty to keep you busy on the property - and those things offer to provide you with instantaneous rewards.
I'm doing LEF male hormone labs (non-ultra PSA) at nearest walk-in location on Thursday, so that should signal any big-time treatment failure to achieve durable status. This will be mid-way to my next MO appt with the more sensitive labs in early Sept. As with all of us on and off treatment, it is forever a work in progress.
Good Luck with the work wrap-up. And keep me posted on your treatment progress. Best to you and Lady M,
I am looking forward to ending my work in 4 days. I have several chores , so fishing has to wait till fall most likely. Best of luck on Thursday. I need to go get an USPSA from LEF sometime next week. I will be doing more research on orexin receptor antagonists, since
one never knows when one might need to change it up....
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Thoughts on next steps
Dose titration for CRPC 
