Evidence map›Paper›PMID 38871731›Full record

ArticleCell death & disease2024

Antipsychotics possess anti-glioblastoma activity by disrupting lysosomal function and inhibiting oncogenic signaling by stabilizing PTEN.

John Ryan Jacob, Kamalakannan Palanichamy, Arnab Chakravarti

Abstract read
In one paragraph

Article in Cell death & disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 1 pooled it
–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

10 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  6. Review
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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

3 authors.

John Ryan JacobDepartment of Radiation Oncology, The Ohio State University College of Medicine and Comprehensive Cancer Center, Columbus, OH, 43210, USA.
Kamalakannan PalanichamyDepartment of Radiation Oncology, The Ohio State University College of Medicine and Comprehensive Cancer Center, Columbus, OH, 43210, USA. kamalakannan.palanichamy@osumc.edu.ORCID 0000-0002-3216-7812
Arnab ChakravartiDepartment of Radiation Oncology, The Ohio State University College of Medicine and Comprehensive Cancer Center, Columbus, OH, 43210, USA.

Funding

Translational Therapeutics Research Program (TT)P30CA016058 · NCI · OHIO STATE UNIVERSITY · PI Tasleem J Padamsee · 1985 to 2026
$132.3M
OSU as a Network Lead Academic Participating Site for the NCI NCTNUG1CA233331 · NCI · OHIO STATE UNIVERSITY · PI John L. Hays, Dwight H. Owen · 2019 to 2026
$8.9M
Genetic evolution of glioblastomas during radiation and temozolomide therapyR01CA188228 · NCI · DANA-FARBER CANCER INST · PI BEROUKHIM, RAMEEN, CHAKRAVARTI, ARNAB · 2015 to 2025
$6.9M
NCI NIH HHS P30 CA016058NCI NIH HHS R01 CA188228NCI NIH HHS UG1 CA233331
6 · The paper itself

Abstract

The repurposing of medications developed for central nervous system (CNS) disorders, possessing favorable safety profiles and blood-brain barrier permeability, represents a promising strategy for identifying new therapies to combat glioblastoma (GBM). In this study, we investigated the anti-GBM activity of specific antipsychotics and antidepressants in vitro and in vivo. Our results demonstrate that these compounds share a common mechanism of action in GBM, disrupting lysosomal function and subsequently inducing lysosomal membrane rupture and cell death. Notably, PTEN intact GBMs possess an increased sensitivity to these compounds. The inhibition of lysosomal function synergized with inhibitors targeting the EGFR-PI3K-Akt pathway, leading to an energetic and antioxidant collapse. These findings provide a foundation for the potential clinical application of CNS drugs in GBM treatment. Additionally, this work offers critical insights into the mechanisms and determinants of cytotoxicity for drugs currently undergoing clinical trials as repurposing agents for various cancers, including Fluoxetine, Sertraline, Thioridazine, Chlorpromazine, and Fluphenazine.

Indexed as

Antipsychotic AgentsGlioblastomaLysosomesPTEN PhosphohydrolaseSignal TransductionAnimalsBrain NeoplasmsCell Line, TumorChlorpromazineDrug RepositioningErbB ReceptorsHumansMiceMice, NudePhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktAntipsychotic AgentsChlorpromazineErbB ReceptorsPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktPTEN PhosphohydrolasePTEN protein, human

Identifiers

PMID38871731
PMCPMC11176297

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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.