Evidence map›Paper›PMID 42090721›Full record

ArticleCancer research communications2026

MAGMAS Inhibition Enhances Temozolomide Efficacy in Chemotherapy-Resistant Glioblastoma Models.

Javier J Lepe, Jennifer D Tran, Naomi Lomeli, Vi P Dang, Valerie C Nguyen, Parthiban Chokkalingam, Sasmita Das, Bhaskar C Das, Daniela A Bota

Abstract read
In one paragraph

Article in Cancer research communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

Javier J Lepe *Department of Experimental Pathology and Laboratory Medicine, University of California, Irvine, Irvine, California.ORCID 0000-0001-8956-6999
Jennifer D Tran *Department of Experimental Pathology and Laboratory Medicine, University of California, Irvine, Irvine, California.ORCID 0009-0006-6238-1285
Naomi LomeliDepartment of Neurology, University of California, Irvine, Irvine, California.ORCID 0000-0002-1071-386X
Vi P DangDepartment of Anatomy and Neurobiology, University of California, Irvine, Irvine, California.ORCID 0009-0009-2398-013X
Valerie C NguyenDepartment of Neurology, University of California, Irvine, Irvine, California.ORCID 0009-0008-8788-3673
Parthiban ChokkalingamDivision of Drug and Biotherapeutic Discovery, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, The State University of New York (SUNY), Buffalo, New York.ORCID 0000-0003-0763-8237
Sasmita DasDivision of Drug and Biotherapeutic Discovery, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, The State University of New York (SUNY), Buffalo, New York.ORCID 0000-0001-7752-2569
Bhaskar C DasDivision of Drug and Biotherapeutic Discovery, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, The State University of New York (SUNY), Buffalo, New York.ORCID 0000-0002-5837-027X
Daniela A BotaDepartment of Experimental Pathology and Laboratory Medicine, University of California, Irvine, Irvine, California.ORCID 0000-0002-9680-9060

Funding

Univ.of Calif., Irvine Cancer Center Support GrantP30CA062203 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI RICHARD A. VAN ETTEN · 1994 to 2026
$57.9M
University of California Health Participation in the National COVID Cohort Collaborative (N3C)UL1TR001414 · NCATS · UNIVERSITY OF CALIFORNIA-IRVINE · PI COOPER, DAN M, VILAIN, ERIC J. · 2015 to 2023
$35.1M
California Institute for Regenerative Medicine (CIRM) TB1-01185National Cancer Institute (NCI) P30CA062203National Institute of Neurological Disorders and Stroke (NINDS) NS111303National Institute of Neurological Disorders and Stroke (NINDS) R01NS109423NCATS NIH HHS UL1 TR001414NCI NIH HHS P30 CA062203
6 · The paper itself

Abstract

Glioblastoma (GBM, isocitrate dehydrogenase wild-type grade 4 astrocytoma) is the most aggressive and common brain tumor, characterized by increased proliferation, invasiveness, mitochondrial-dependent changes, and necrosis. GBM recurrence is universal despite the standard-of-care treatment with maximal surgical resection, radiation, and temozolomide (TMZ). Most patients relapse 6 to 9 months following initial diagnosis, and the median survival after recurrence is less than a year. Therefore, effective therapeutic strategies are needed to overcome glioma resistance mechanisms and improve long-term outcomes for patients with GBM. Mitochondria-associated granulocyte macrophage colony-stimulating factor molecule (MAGMAS, PAM16) is a nuclear-encoded mitochondrial protein subunit of the translocase of the inner membrane 23 complex that functions as an essential regulator of protein trafficking into the mitochondrial matrix. We previously demonstrated that MAGMAS is overexpressed in GBM and that the small-molecule MAGMAS inhibitor BT9 reduces mitochondrial respiration and is cytotoxic to glioma cells in vitro. In this study, we investigated the role of MAGMAS in GBM biology and the effects of MAGMAS inhibition on TMZ-resistant glioma lines and patient-derived glioma stem-like cells. We observed elevated PAM16 levels in recurrent GBM, chemoresistant glioma cells, and during metabolic switching processes. Concurrent treatment with BT9 and TMZ significantly increased cell death compared with either drug alone in all glioma lines, irrespective of their TMZ resistance status. Additionally, GBM cells constitutively expressing shPAM16 became sensitized to TMZ both in vitro and in vivo in an intracranial xenograft model. Our findings suggest that targeting MAGMAS holds promise as a novel, effective therapeutic strategy for GBM. SIGNIFICANCE: This study finds a link between mitochondrial protein MAGMAS and chemotherapy resistance in glioma central nervous system cancers. These findings can help improve our understanding of how mitochondria play an important role in chemotherapy resistance mechanisms - highlighting MAGMAS as a target to help enhance the efficacy of TMZ in chemotherapy resistance cells.

Indexed as

Brain NeoplasmsDrug Resistance, NeoplasmGlioblastomaGranulocyte-Macrophage Colony-Stimulating FactorTemozolomideAnimalsAntineoplastic Agents, AlkylatingCell Line, TumorHumansMiceMitochondriaMitochondrial Precursor Protein Import Complex ProteinsXenograft Model Antitumor AssaysAntineoplastic Agents, AlkylatingGranulocyte-Macrophage Colony-Stimulating FactorMitochondrial Precursor Protein Import Complex ProteinsPAM16 protein, humanTemozolomide

Identifiers

PMID42090721
PMCPMC13247981

What Socratic holds

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LicenceCC BY
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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 Socratic graph.