bims-netuvo Biomed News
on Nerves in tumours of visceral organs
Issue of 2025–06–22
two papers selected by
Maksym V. Kopanitsa, Charles River Laboratories
  1. Molecular drivers in CNS metastatic disease.
  2. Beta-blockers prolong response to androgen deprivation therapy in prostate cancer through modulation of the neuro-immuno-oncology axis.
  1. Adv Cancer Res. 2025 ;pii: S0065-230X(25)00004-1. [Epub ahead of print]165 1-56
    Molecular drivers in CNS metastatic disease.
    Hannah Kim, Sofia Chernet, Priya Kumthekar, Akanksha Sharma.
      The incidence and prevalence of CNS metastases of systemic cancer is only increasing worldwide, especially as our available systemic therapies have improved, resulting in longer survival and more time to allow for CNS progression. Fortunately, we have made substantial therapeutic advances in drug development in the last decade, with newer agents demonstrating significant penetration into the nervous system and notable efficacy. Treatments specifically targeted for certain mutations in the cancer pathway have been especially successful in aborting the onward trajectory and growth of cancer cells in the nervous system. In this review, we provide an overview and update of the drugs that have demonstrated benefit in achieving intracranial control (at times including leptomeningeal disease), many of which have already received or are pending regulatory approval. We also provide a brief look into the landscape of ongoing clinical research including challenges in the field.
    Keywords:  Blood brain barrier; CNS metastases; Genetic mutations; Immunotherapy; Leptomeningeal disease; Molecular markers; Targeted therapy
    DOI:  https://doi.org/10.1016/bs.acr.2025.04.004
  2. J Transl Med. 2025 Jun 17. 23(1): 672
    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, Matti Poutanen, Betina Katz, Bente Halvorsen, Gunhild Mari Mælandsmo, Kristin Austlid Taskén.
       BACKGROUND: The 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.
    METHODS: An 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.
    RESULTS: A 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.
    CONCLUSION: The 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.
    Keywords:  Androgen receptor; Beta-adrenergic receptor; Castration-resistant prostate cancer; Oxidative phosphorylation; PI3K/AKT/mTOR; Pro-inflammatory; SRC
    DOI:  https://doi.org/10.1186/s12967-025-06644-7
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