Evidence map›Paper›PMID 40528241›Full record

ArticleJournal of translational medicine2025

Beta-blockers prolong response to androgen deprivation therapy in prostate cancer through modulation of the neuro-immuno-oncology axis.

Malin Hagberg Thulin, Håkon Ramberg, Heidi Kristin Nielsen, Helene Hartvedt Grytli, Shivanthe Sivanesan, Abhilash D Pandya, Kotryna Seip, Kjetil Wessel Andressen, Anna Linder, Miriam Øijordsbakken and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

  1. Neuroscience in prostate cancer.Prostate cancer and prostatic diseases · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Malin Hagberg Thulin *Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at the Sahlgrenska Academy, University of Gothenburg, Vita Stråket 11, 403 45, Gothenburg, Sweden.
Håkon Ramberg *Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, Nydalen, P.O. Box 4950, 0424, Oslo, Norway.
Heidi Kristin NielsenDepartment of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, Nydalen, P.O. Box 4950, 0424, Oslo, Norway.
Helene Hartvedt GrytliDepartment of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, Nydalen, P.O. Box 4950, 0424, Oslo, Norway.
Shivanthe SivanesanDepartment of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, Nydalen, P.O. Box 4950, 0424, Oslo, Norway.
Abhilash D PandyaDepartment of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, Nydalen, P.O. Box 4950, 0424, Oslo, Norway.
Kotryna SeipDepartment of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, Nydalen, P.O. Box 4950, 0424, Oslo, Norway.
Kjetil Wessel AndressenInstitute of Clinical Medicine, University of Oslo, Oslo, Norway.
Anna LinderSahlgrenska Center for Cancer Research, Department of Obstetrics and Gynecology, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, 413 90, Gothenburg, Sweden.
Miriam ØijordsbakkenDepartment of Medical Biochemistry, Oslo University Hospital, Oslo, Norway.
Matti PoutanenDepartment of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at the Sahlgrenska Academy, University of Gothenburg, Vita Stråket 11, 403 45, Gothenburg, Sweden.
Betina KatzDepartment of Pathology, Oslo University Hospital, Oslo, Norway.
Bente HalvorsenInstitute of Clinical Medicine, University of Oslo, Oslo, Norway.
Gunhild Mari MælandsmoDepartment of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, Nydalen, P.O. Box 4950, 0424, Oslo, Norway.
Kristin Austlid TaskénDepartment of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, Nydalen, P.O. Box 4950, 0424, Oslo, Norway. k.a.tasken@medisin.uio.no.ORCID 0000-0001-5530-4915

Funding

Cancerfonden 21 1889 PjKreftforeningen 181720Kreftforeningen 5724658Stiftelsen Assar Gabrielssons Fond FB23-105Wellcome Trust 206202
6 · The paper itself

Abstract

backgroundThe therapeutic impact of beta-blockers (BB), beta-adrenergic receptor antagonists, on prostate cancer remains controversial. The underlying health conditions of BB users complicate the ability to isolate and evaluate the specific effects of these drugs on the tumour cells. This study investigated whether BBs, by inhibiting sympathetic nerve signalling, extended the duration of androgen deprivation therapy (ADT) effectiveness in patients with de novo metastatic hormone sensitive prostate cancer and in prostate cancer xenograft models, while also uncovering the molecular mechanisms involved.

methodsAn analysis was conducted on prospectively collected data from the Cancer Registry of Norway, Norwegian Prescription Database, and Norwegian Cause of Death Registry focusing on patients with de novo metastatic prostate cancer undergoing ADT using the commencement of second-line treatment as the endpoint. In addition, the causal effect of BB treatment was studied in two different hormone-sensitive prostate cancer xenograft mouse models. Prior to treatment, mice were surgically castrated, to mimic ADT, and tumour progression was tracked by measuring serum PSA levels. RNA sequencing was performed on xenografted orthotopic tumours to investigate the underlying mechanisms, utilizing annotation based on human data and protein levels were validated by the Protein Simple Immunoassay. Immune-related effects were evaluated using immunohistochemistry on tumour tissue and measuring neopterin levels, along with 92 analytes, using the OLINK proximity extension assay on serum samples from xenografted mice and prostate cancer patients, both BB users and non-users.

resultsA competitive risk analysis indicated that BB treatment postponed the initiation of second-line treatment in prostate cancer patients on ADT. Additionally, in both prostate cancer xenograft models, BB treatment reduced tumour burden and delayed progression to castration-resistant prostate cancer. Mechanistically, BB treatment suppressed androgen receptor signalling and induced a metabolic shift by up-regulating oxidative phosphorylation transcripts and down-regulating those involved in fatty acid synthesis and the PI3K/AKT/mTOR pathway. Additionally, BB treatment increased serum pro-inflammatory cytokines, such as the IL23/IL17 axis, in both xenografted mice and in patient samples. Enhanced intra-tumoral CD68+ immune cell infiltration was also observed in the tumours.

conclusionThe data suggest that BB combined with ADT delay the progression to castration-resistant prostate cancer. This may be achieved by influencing androgen receptor activity, adjusting energy metabolism and fostering a pro-inflammatory antitumoral microenvironment.

Indexed as

Adrenergic beta-AntagonistsAndrogen AntagonistsAndrogensProstatic NeoplasmsAnimalsCell Line, TumorHumansMaleMiceSignal TransductionXenograft Model Antitumor AssaysAdrenergic beta-AntagonistsAndrogen AntagonistsAndrogensAndrogen receptorBeta-adrenergic receptorCastration-resistant prostate cancerOxidative phosphorylationPI3K/AKT/mTORPro-inflammatorySRC

Identifiers

PMID40528241
PMCPMC12175445

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.