Evidence map›Paper›PMID 40784667›Full record

ArticleFundamental & clinical pharmacology2025

Repurposing Asparaginase Therapy to Target Cisplatin-Resistant Cancer Cells.

Jiantao Wang, Nasim Pouryaghoub, Robert Strauss, Jiri Bartek, Si Min Zhang, Sean G Rudd

Abstract read
In one paragraph

Article in Fundamental & clinical pharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
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

6 authors.

Jiantao WangScience for Life Laboratory (SciLifeLab), Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
Nasim PouryaghoubScience for Life Laboratory (SciLifeLab), Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
Robert StraussDanish Cancer Institute, Genome Integrity Group, Copenhagen, Denmark.ORCID https://orcid.org/0000-0003-1777-7177
Jiri BartekDanish Cancer Institute, Genome Integrity Group, Copenhagen, Denmark.
Si Min ZhangScience for Life Laboratory (SciLifeLab), Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
Sean G RuddScience for Life Laboratory (SciLifeLab), Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.ORCID https://orcid.org/0000-0002-4368-3855

Funding

Åke Wiberg Stiftelse M22-0011Åke Wiberg Stiftelse M23-0088Barncancerfonden PR2019-0014Barncancerfonden PR2022-0003Cancerfonden 19-0056-JIACancerfonden 20-0879-PjCancerfonden 23-2782-PjDanish Cancer Society R322-A17482Fabrikant Chas. Otzen's FondKarolinska InstitutetKøbmand Niels Erik Munk Pedersen FondenStiftelsen Clas Groschinskys Minnesfond M2353Stiftelsen Clas Groschinskys Minnesfond M2449Vetenskapsrådet 2018-02114Vetenskapsrådet VR-MH 2014-46602-117891-30West China Hospital, Sichuan University
6 · The paper itself

Abstract

backgroundCisplatin and its derivatives remain a cornerstone in the treatment of solid malignancies. Resistance is a major factor limiting their clinical utility.

objectivesIn the present study, we set out to interrogate therapeutic approaches to target cisplatin-resistant cancer cells. We focused on therapies exploiting metabolic pathways that are altered in drug-resistant cells. We sought to find an existing therapy that has monotherapy efficacy against cisplatin-resistant cancer cells that can also re-sensitize to cisplatin.

methodsWe used lung and ovarian cancer cell lines with acquired resistance to cisplatin together with drug sensitivity assays, conducted both with monotherapies and cisplatin combinations.

resultsWe show that cancer cell lines with acquired resistance to cisplatin have altered levels of enzymes involved in glutamine metabolism, which can result in differential sensitivity to targeted agents. We show that expression of one of these enzymes-the glutamate-cystine antiporter SLC7A11, up-regulated 6-fold in a cisplatin-resistant lung cancer cell line-has potential prognostic significance in lung cancer but not ovarian cancer. After identifying a common dependency of cisplatin-resistant cancer cells upon extracellular glutamine, we then evaluate the utility of the long-standing anti-leukemic therapy asparaginase (ASNase)-which possesses both asparaginase and glutaminase activity-as a potential approach. We show ASNase preferentially inhibits the proliferation of cisplatin-resistant cancer cells and can potentially re-sensitize these cells to cisplatin.

conclusionsOur results underpin the prevalence of altered metabolism in cisplatin-resistant cells and highlight the potential utility of re-purposing ASNase to target these cells, warranting further investigation.

Indexed as

Antineoplastic AgentsAsparaginaseCisplatinDrug Resistance, NeoplasmLung NeoplasmsOvarian NeoplasmsAmino Acid Transport System y+Cell Line, TumorCell ProliferationDrug RepositioningFemaleGlutamineHumansAmino Acid Transport System y+Antineoplastic AgentsAsparaginaseCisplatinGlutamineSLC7A11 protein, humanasparaginase (ASNase)chemoresistancecisplatinglutaminemetabolic rewiringSLC7A11

Identifiers

PMID40784667
PMCPMC12335911

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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.