Prolactin

[Tnjw]

Have shared the possibility of prolactin feeding advanced pc with mo/urologist . Dr's found the possibility of lowering prolactin interesting but have never heard of anyone using in their practice. If anyone can advise of a doctor using this in their protocol please reply so I can share with my doctors. They have reached out to piers but none have ever used lowering prolactin in treating pc

[Tall_Allen]

I think the idea of inhibiting the prolactin receptors was abandoned when a Phase 1 trial showed no activity:

ar.iiarjournals.org/content...

[Tnjw in reply to Tall_Allen]

Thanks T A

[Purple-Bike in reply to Tall_Allen]

It was mot valuable to see this study, that again shows the limits of promising in vitro and in vivo studies, that fail to translate into clinical benefit.

From the study. "Dose escalation was halted because no responses were observed either in this study or in the parallel phase I study (from prolactin suppression). Preclinical evidence suggests that prolactin signaling has an important role in breast and prostate cancer, and LFA102 treatment did elicit tumor shrinkage in an in vivo breast cancer model (19). The situation in the clinic is clearly different, since LFA102 seemed to have no efficacy as a single agent in patients with advanced breast cancer or CRPC.

Prolactin suppression could possibly even promote some tumors:

"Potential explanations for the lack of efficacy (of prolactin suppression) might include the possibility that prolactin is not an oncogenic driver in human breast or prostate cancer, that other pathways are activated in order to bypass the effect of PRLR inhibitors, or that prolactin-independent signaling pathways are upregulated in order to maintain tumors. Although many preclinical studies have demonstrated that PRLR activation can promote cancer cell proliferation and survival (1, 16, 17), the clinical effect of cancer cell-derived prolactin on patient outcome is controversial in recent reports. High PRLR expression was associated with a shorter time to bone metastasis in one study of patients with breast cancer (26), whereas other reports showed that it was associated with better relapse-free survival and longer distant metastasis-free survival (27, 28). Recently it has also been reported that PRLR is a marker of good prognosis in triple-negative breast cancer patients who underwent surgery (29). In line with these reports, expression/activation of Stat5a, an effector molecule in prolactin signaling, was positively correlated with an increased level of histologic differentiation in breast cancer tissues and with a favorable prognosis (30). Thus, whereas prolactin may contribute to the initial development of breast cancer, it may also have context-specific roles in restricting the metastatic potential of certain tumors (31)".

I was just to reorder cabergoline thankfully I know better now.

[Tnjw in reply to Purple-Bike]

Thank you for your reply

[32Percenter]

This study from 1977 showed a beneficial effect among about half the metastatic men treated with L-Dopa (lowers prolactin), but the study was with a very small group:

sciencedirect.com/science/a...

An Italian study from 2005:

google.com/url?sa=t&source=...

Here's some Mexican research from 2010:

medigraphic.com/cgi-bin/new...

Another Italian study in 2019, this one finding that PCa patients with low prolactin levels were MORE likely to experience extra-capsular spread of the cancer:

karger.com/uin/article-abst...

And of course, Dr. Leslie C. Costello's recent work studying this:

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

pubmed.ncbi.nlm.nih.gov/312....

These are only a few of the research studies out there, and overall it seems to be a mixed bag. It may be that only certain prostate cancer cell lines are affected by prolactin suppression. With regards to the prolactin inhibitor trial showing no effect, it could be that suppression of prolactin levels should be the goal, rather than blocking it at the receptor. As in prolactin activity in some other manner downstream may be to blame, rather than activity directly at the receptor. I'd like to see more research looking at this, because clearly in certain instances, suppressing prolactin seems to help.

In any case Tnjw, if you're looking for a practitioner or researcher to consult, the one most interested in this area of study would probably be Dr. Costello:

researchgate.net/profile/Le...

[Tnjw in reply to 32Percenter]

Thank for your reply and references. My thoughts exactly on the suppression of total prolactin levels as opposed to receptor blockage. I had read that Dr Myers wanted prolactin levels to be maintained below 3 ng/ml . I will continue to try to research and perhaps reach out to Dr Costello. Thanks again. Tn/ Jw