Evidence map›Paper›PMID 41244832›Full record

ArticleFrontiers in pharmacology2025

The RET inhibitor pralsetinib suppresses TMZ-resistant glioma growth by regulating spermine production.

Lingyun Ma, Hang Gong, Wei Sun, Jialing Deng, Qinghua Zhang, Jianzhao Niu, Huimin Sun, Xue Han, Tingting Du, Nina Xue and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Frontiers in pharmacology, 2025. 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
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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

12 authors.

Lingyun Ma *NMPA Key Laboratory for Quality Research and Evaluation of Chemical Drugs, National Institutes for Food and Drug Control, Beijing, China.
Hang Gong *Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Wei Sun *Department of Neurology, Ningguo City People's Hospital, Ningguo, China.
Jialing DengDepartment of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Qinghua ZhangDepartment of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Jianzhao NiuNMPA Key Laboratory for Quality Research and Evaluation of Chemical Drugs, National Institutes for Food and Drug Control, Beijing, China.
Huimin SunNMPA Key Laboratory for Quality Research and Evaluation of Chemical Drugs, National Institutes for Food and Drug Control, Beijing, China.
Xue HanNational Engineering Research Center for the Development of New Drugs, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Tingting DuDepartment of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Nina XueDepartment of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Ming JiNational Engineering Research Center for the Development of New Drugs, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Qian LiuNMPA Key Laboratory for Quality Research and Evaluation of Chemical Drugs, National Institutes for Food and Drug Control, Beijing, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Objective: Glioma is the most common malignant tumor of the central nervous system and is characterized by altered cellular metabolism. Although temozolomide (TMZ)-based adjuvant treatment has improved overall patient survival, clinical outcomes remain unsatisfactory. TMZ resistance is a major contributing factor. The mechanisms underlying TMZ resistance are highly complex. This study aimed to elucidate the role of spermine in TMZ resistance and to assess the antitumor activity of kinase inhibitors against TMZ-resistant glioma. Methods: The TCGA data from glioma patients treated with TMZ was analyzed and metabolomic analysis of both TMZ-sensitive and TMZ-resistant glioma cells was performed. A series of compounds in both TMZ-sensitive and TMZ-resistant glioma cells were screened, and their brain penetration capacity was tested by MacroFlux assay. The antitumor activity of pralsetinib was evaluated Results: In this study, we found that spermine synthase (SMS) was highly expressed in gliomas that showed a poor clinical response to TMZ treatment. Spermine, the metabolic product of SMS, was also elevated in TMZ-resistant glioma cells and promoted their proliferation. Further investigation revealed that pralsetinib, a selective RET inhibitor, exhibited significant antitumor activity against TMZ-resistant glioma cells both Conclusion: Our findings reveal the role of spermine in TMZ-resistant glioma and suggest a potential new pharmacological application for pralsetinib in the glioma treatment.

Indexed as

GliomaPralsetinibSpermineSpermine SynthaseTMZ resistance

Identifiers

PMID41244832
PMCPMC12615384

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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.