Evidence map›Paper›PMID 39680480›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025

Addressing Clinical Limitations of Glutaminase Inhibitors: Novel Strategies for Osimertinib-Resistant Lung Cancer by Exploiting Glutamine Metabolic Dependency.

Jiali Huang, Xiankang Zhang, Hui Zhang, Yu Li, Huidan Huang, Zhiyu Li, Zhixia Qiu, Hongxi Wu, Dechun Huang, Xi Xu and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing 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

9 citing papers in PubMed.

  1. Review
  2. [Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2026
    Article
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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

11 authors.

Jiali HuangJiangsu Key Laboratory of Drug Design and Optimization, Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing, Jiangsu, 210009, China.
Xiankang ZhangJiangsu Key Laboratory of Drug Design and Optimization, Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing, Jiangsu, 210009, China.
Hui ZhangJiangsu Key Laboratory of Drug Design and Optimization, Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing, Jiangsu, 210009, China.
Yu LiJiangsu Key Laboratory of Drug Design and Optimization, Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing, Jiangsu, 210009, China.
Huidan HuangCenter of Drug Screening & Evaluation, Wannan Medical College, Wuhu, Anhui, 241000, China.
Zhiyu LiJiangsu Key Laboratory of Drug Design and Optimization, Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing, Jiangsu, 210009, China.
Zhixia QiuJiangsu Key Laboratory of Drug Design and Optimization, Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing, Jiangsu, 210009, China.
Hongxi WuJiangsu Key Laboratory of Drug Design and Optimization, Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing, Jiangsu, 210009, China.
Dechun HuangDepartment of Biomedical Engineering, School of Engineering, China Pharmaceutical University, Nanjing, Jiangsu, 210009, China.
Xi XuJiangsu Key Laboratory of Drug Design and Optimization, Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing, Jiangsu, 210009, China.
Jinlei BianJiangsu Key Laboratory of Drug Design and Optimization, Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing, Jiangsu, 210009, China.ORCID https://orcid.org/0000-0003-4552-1195

Funding

"Double First-Class" university project CPUQNJC22 05National Natural Science Foundation of China 82073702National Natural Science Foundation of China 8210131471National Natural Science Foundation of China 82204238National Natural Science Foundation of China 82373740National Natural Science Foundation of China 82473784Natural Science Foundation of Jiangsu Province for Excellent Young Scientists BK20211580
6 · The paper itself

Abstract

Overcoming acquired resistance to Osimertinib remains a critical challenge in treating NSCLC. This research indicates that Osimertinib-resistant cells exhibit a strong dependence on glutamine metabolism. However, targeting GLS1 shows limited anticancer effects, probably because it cannot fully block the glutamine metabolic pathway. The investigation reveals that a more effective strategy involves simultaneously inhibiting both ASCT2 and GLS1. After confirming the efficacy of this dual-targeting approach against Osimertinib-resistant cells in preclinical models, the potential of utilizing a broad-spectrum glutamine metabolism antagonist is further explored to achieve superior antitumor efficacy. DON, broad-spectrum glutamine antagonist, presents toxicity issues. Herein, the high NQO1 expression in Osimertinib-resistant NSCLC cells is leveraged to design an NQO1-responsive DON prodrug, 10e (LBJ-10e). This prodrug demonstrates superior safety compared to natural DON and greater antitumor activity against resistant tumors compared to the clinical phase II drug DRP104. These findings may address the clinical limitations of GLS1 allosteric inhibitors and underscore prodrug strategies in effectively treating Osimertinib-resistant lung cancer, providing a foundation for future clinical trials.

Indexed as

AcrylamidesAniline CompoundsCarcinoma, Non-Small-Cell LungDrug Resistance, NeoplasmGlutaminaseGlutamineLung NeoplasmsAnimalsAntineoplastic AgentsCell Line, TumorHumansIndolesMiceMice, NudePyrimidinesXenograft Model Antitumor AssaysAcrylamidesAniline CompoundsAntineoplastic AgentsGlutaminaseGlutamineIndolesosimertinibPyrimidinesdrug designglutamineNQO1NSCLCOsimertinib resistance

Identifiers

PMID39680480
PMCPMC11809341

What OpenQuestion holds

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Registered trials

None linked

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.