Evidence map›Paper›PMID 40464376›Full record

ArticleeLife2025

Targeting SLC7A11-mediated cysteine metabolism for the treatment of trastuzumab-resistant HER2-positive breast cancer.

Yijia Hua, Ningjun Duan, Chunxiao Sun, Fan Yang, Min Tian, Yanting Sun, Shuhan Zhao, Jue Gong, Qian Liu, Xiang Huang and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in eLife, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

  1. Review
  2. Review
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  4. Review
  5. Review
  6. Metabolic hallmarks of trastuzumab resistance.Expert opinion on therapeutic targets · 2025
    Review
  7. Review
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

14 authors.

Yijia Hua *Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.ORCID https://orcid.org/0009-0006-4323-8715
Ningjun Duan *Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.ORCID https://orcid.org/0000-0001-6316-3796
Chunxiao SunDepartment of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Fan YangDepartment of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Min TianDepartment of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Yanting SunDepartment of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Shuhan ZhaoDepartment of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Jue GongDepartment of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Qian LiuDepartment of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Xiang HuangDepartment of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Yan LiangDepartment of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Ziyi FuDepartment of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Wei LiDepartment of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Yongmei YinDepartment of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.ORCID https://orcid.org/0000-0003-3335-369X

Funding

Beijing Xisike Clinical Oncology Research Foundation Y-2019AZZD-00680High-level Innovation Team of Nanjing Medical University Program JX102GSP201727National Natural Science Foundation of China 81972484National Natural Science Foundation of China 82203488National Natural Science Foundation of China 82272667The Collaborative Innovation Center for Tumor Individualization Program JX21817902/008
6 · The paper itself

Abstract

Trastuzumab resistance remains a challenge for HER2-positive breast cancer treatment. Targeting metabolic reprogramming would provide novel insights for therapeutic strategies. Here, we integrated metabolomics, transcriptomics, and epigenomics data of trastuzumab-sensitive and primary-resistant HER2-positive breast cancer to identify metabolic alterations. Aberrant cysteine metabolism was discovered in trastuzumab primary-resistant breast cancer at both circulating and intracellular levels. The inhibition of SLC7A11 and cysteine starvation could synergize with trastuzumab to induce ferroptosis. Mechanistically, increased H3K4me3 and decreased DNA methylation enhanced SLC7A11 transcription and cystine uptake in trastuzumab-resistant breast cancer. The regulation of epigenetic modifications modulated cysteine metabolism and ferroptosis sensitivity. These results revealed an innovative approach for overcoming trastuzumab resistance by targeting specific amino acid metabolism.

Indexed as

Amino Acid Transport System y+Antineoplastic Agents, ImmunologicalBreast NeoplasmsCysteineDrug Resistance, NeoplasmErb-b2 Receptor Tyrosine KinasesTrastuzumabCell Line, TumorDNA MethylationFemaleFerroptosisHumansAmino Acid Transport System y+Antineoplastic Agents, ImmunologicalCysteineERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesSLC7A11 protein, humanTrastuzumabcancer biologycysteine metabolismepigenetic modificationsHER2-positive breast cancerhumanmousetrastuzumab primary resistance

Identifiers

PMID40464376
PMCPMC12136593

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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.