Malecare newsletter reports Finish study glucocorticoids (e.g. prednisone, prednisolone, dexamethasone) can lead to castrate resistance

[Graham49]

“However, recent studies have shown that the glucocorticoid receptor also has an oncogenic, or cancer-promoting, effect in cancers like breast and prostate cancer. In prostate cancer, the glucocorticoid receptor can replace the activity of the androgen receptor, which is main oncogenic factor in this cancer, when its activity is inhibited by drug therapy. Thus, glucocorticoids help prostate cancer develop resistance to drug therapy.”

University of Eastern Finland. "New insight into combating drug-resistant prostate cancer." ScienceDaily. ScienceDaily, 10 April 2024 sciencedaily.com/releases/2...

Journal References:

Jasmin Huttunen, Niina Aaltonen, Laura Helminen, Kirsi Rilla, Ville Paakinaho. EP300/CREBBP acetyltransferase inhibition limits steroid receptor and FOXA1 signaling in prostate cancer cells. Cellular and Molecular Life Sciences, 2024; 81 (1) DOI: 10.1007/s00018-024-05209-z

Laura Helminen, Jasmin Huttunen, Melina Tulonen, Niina Aaltonen, Einari A Niskanen, Jorma J Palvimo, Ville Paakinaho. Chromatin accessibility and pioneer factor FOXA1 restrict glucocorticoid receptor action in prostate cancer. Nucleic Acids Research, 2024; 52 (2): 625 DOI: 10.1093/nar/gkad1126

[Tall_Allen]

You misinterpreted that.

[Graham49 in reply to Tall_Allen]

Please enlighten me with the correct interpretation.

[Tall_Allen in reply to Graham49]

Glucocorticoids are known to have a short-lived PCa-inhibiting effect:

ncbi.nlm.nih.gov/pmc/articl...

[Grandpa4 in reply to Tall_Allen]

In the study they found that glucocorticoids could deliver a growth promoting effect to prostate cancer cells in culture and promote the growth of resistant cells. Your study and their study could both be right. They inhibit normal cells briefly but promote resistant cells long term. It was done with cells in tissue so it might not transfer to intact being.

[4tunate1 in reply to Tall_Allen]

Tall_Allen - I'm not clear of the role of prednisone in my care (Lupron every six months, Abiraterone 1000mg daily, prednisone 5mg daily. Can you share some insight on the purpose of the prednisone? I thought I had read it helps with stomach issues that arise from taking the oral Abiraterone?

[gsun in reply to 4tunate1]

Abi inhibits the production of cortisol. Prednisone mimics cortisol so we don't feel crappy due to the lack of cortisol.

[MomOfMaisy in reply to 4tunate1]

We were told that the prednisone replaces the lost cortisol in the body. My husband who is castrate sensitive takes 1,000 mg abiraterone daily and 5 mg. prednisone as well as an Eligard injection every 3 months.

[Graham49 in reply to Tall_Allen]

Unfortunately the study you referenced does not give me confidence that “Glucocorticoids are known to have a short-lived PCa-inhibiting effect”. Although there are some mitigating factors.

“First, patients with CRPC treated in randomized studies with glucocorticoids do not appear to have dramatic decrement in functional status with treatment initiation, and in some cases have PSA responses and symptomatic improvement, suggesting that glucocorticoids are not driving an adverse biology in the majority of patients with CRPC. Second, the number of patients who demonstrate glucocorticoid withdrawal responses appears limited, although this has not been closely evaluated. Third, very limited information is currently available from tissue samples acquired directly from patients with CRPC to suggest that GR upregulation or mutation of AR is a frequent event. Further studies are necessary to answer the question of whether glucocorticoids or GR are mediating progression in specific subsets of patients with CRPC. It will be important to determine the frequency of GR upregulation, as well as activating AR mutations in the ongoing analyses of CRPC using exome sequencing and RNAseq through the efforts of the AACR-PCR-SU2C dream teams”

And from the second Finish study:

“Thus, GR can act either as a tumor suppressor or as an oncogene, likely depending on the cellular context. Intriguingly, PCa cells display a distinct expression of GR (16,57), with the highest expression at the AR-negative stem cell-like and neuroendocrine subtypes. Thus, GR likely has an extensive role in AR-negative PCa subtypes which warrants further investigation, especially since these subtypes represent around half of the PCa patients (57). “

[Maxone73 in reply to Graham49]

I simply hate studies (and they are the majority) where "XYZ can act either as a tumor suppressor or as an oncogene"...darn!

[garyjp9 in reply to Tall_Allen]

TA, how should we interpret this? Looking at this and related studies, it sounds like they are saying that the longer you take gluticosteroids, the more likely they are to go from inhibiting PC to becoming oncogenic. Say it ain't so! I was unaware this was even a topic of discussion.

[Tall_Allen in reply to garyjp9]

It ain't so. As I said, Glucocorticoids are known to have a short-lived PCa-inhibiting effect. Read this:

ncbi.nlm.nih.gov/pmc/articl...

Patients who go off half-cocked over lab studies do themselves a disservice. That they alarm others with weak evidence is sinful, in my way of thinking.

Also, consider that most men with prostate cancer only take a replacement dose of prednisone to replace what is taken away by abiraterone. Your body needs cortisol (or biosimilar) to function. You would die without it.

Other uses of prednisone are temporary to mitigate side effects of chemo or to interrupt inflammation from radiation.

No one takes prednisone if they don't need it.

[MomOfMaisy in reply to Tall_Allen]

This is what my husband was told. The prednisone replaces the lost cortisol brought on by the abiraterone.

[garyjp9 in reply to Tall_Allen]

Thank you, TA. The 2014 article was one of the ones I saw before asking my question. Despite not understanding much of it, I was concerned about some of the comments in the section entitled: "GLUCOCORTICOID-STIMULATED TUMOR GROWTH THROUGH NUCLEAR RECEPTOR INTERACTIONS." After 2.5 years on prednisone with Abiraterone, I'm now on long term hydrocortisone for secondary adrenal insufficiency (also intended to replace missing cortisol), so this discussion caught my attention.

[Graham49 in reply to Tall_Allen]

This is the same paper that you posted before. How does it disprove the Finish studies?

[CousinGrandpa]

the correct link is sciencedaily.com/releases/2...

[London441]

This is a waste of time. Many beneficial drugs have possibility of adverse effects directly related to the disease they are treating, or in this case accompanying.

Usually the association is either false or unproven at best. If it is true, it is typically minimal compared to not taking it, and well worth the trade. Further, revealing any actual proof of such almost always takes a very long time-longer than any of us can afford.

Not taking steroids with abiraterone can be very dangerous, far beyond ‘feeling crappy’, Try not taking prednisone with it and let me know how that works for you.