Evidence map›Paper›PMID 39856383›Full record

ArticleClinical & experimental metastasis2025

Repurposing neuroleptics: clozapine as a novel, adjuvant therapy for melanoma brain metastases.

Tobias Wikerholmen, Erlend Moen Taule, Emma Rigg, Birgitte Feginn Berle, Magnus Sættem, Katharina Sarnow, Halala Sdik Saed, Terje Sundstrøm, Frits Thorsen

Abstract read
In one paragraph

Article in Clinical & experimental metastasis, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
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

9 authors.

Tobias WikerholmenDepartment of Biomedicine, University of Bergen, Jonas Lies Vei 91, Bergen, 5009, Norway.ORCID 0000-0002-2925-6144
Erlend Moen TauleDepartment of Biomedicine, University of Bergen, Jonas Lies Vei 91, Bergen, 5009, Norway.ORCID 0000-0002-9182-777X
Emma RiggDepartment of Biomedicine, University of Bergen, Jonas Lies Vei 91, Bergen, 5009, Norway.ORCID 0000-0003-3824-2040
Birgitte Feginn BerleDepartment of Biomedicine, University of Bergen, Jonas Lies Vei 91, Bergen, 5009, Norway.ORCID 0009-0009-9095-1910
Magnus SættemDepartment of Biomedicine, University of Bergen, Jonas Lies Vei 91, Bergen, 5009, Norway.ORCID 0009-0002-7535-7656
Katharina SarnowDepartment of Biomedicine, University of Bergen, Jonas Lies Vei 91, Bergen, 5009, Norway.ORCID 0000-0002-6091-5689
Halala Sdik SaedDepartment of Biomedicine, University of Bergen, Jonas Lies Vei 91, Bergen, 5009, Norway.ORCID 0009-0009-6200-8239
Terje SundstrømDepartment of Neurosurgery, Haukeland University Hospital, Haukelandsveien 22, Bergen, 5021, Norway.ORCID 0000-0002-6503-7141
Frits ThorsenDepartment of Biomedicine, University of Bergen, Jonas Lies Vei 91, Bergen, 5009, Norway. Frits.thorsen@uib.no.ORCID 0000-0002-7762-3703

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The blood-brain barrier and the distinct brain immunology provide challenges in translating commonly used chemotherapeutics to treat intracranial tumors. Previous reports suggest anti-tumoral effects of antipsychotics, encouraging investigations into potential treatment effects of neuroleptics on brain metastases. For the first time, the therapeutic potential of the antipsychotic drug clozapine in treating melanoma brain metastases (MBM) was investigated using three human MBM cell lines. Through in vitro cell culture and viability experiments, clozapine displayed potent anti-tumoral effects on MBM cells with an exploitable therapeutic window when compared to normal human astrocytes or rat brain organoids. Further, it was shown that clozapine inhibited migration, proliferation, and colony formation in a dose-dependent manner. Through flow cytometry and proteome screening, we found that clozapine induced apoptosis in MBM cells and potentially altered the tumor immunological environment by upregulating proteins such as macrophage inflammatory protein-1 alpha (MIP-1α) and interleukin-8 (IL-8). In conclusion, clozapine shows significant and selective anti-tumoral effects on MBM cell lines in vitro. Further in vivo experiments are warranted to translate these results into clinical use.

Indexed as

Antipsychotic AgentsBrain NeoplasmsClozapineDrug RepositioningMelanomaAnimalsApoptosisCell Line, TumorCell MovementCell ProliferationChemotherapy, AdjuvantHumansRatsAntipsychotic AgentsClozapineAntipsychoticsBrain tumorCancerClozapineDrug-repurposingMelanomaMetastasesNeuroleptic

Identifiers

PMID39856383
PMCPMC11761981

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Registered trials

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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 OpenQuestion graph.