Evidence map›Paper›PMID 41148486›Full record

ArticleHuman cell2025

TPM3-NTRK1 fusion confers resistance to osimertinib in lung adenocarcinoma: a model in a continuous cell line.

Fang Cao, Jiayin Dai, Kun Dong, Zhenli Yang, Yanli Zhu, Changsong Qi, Dongmei Lin, Xiaocui Bian, Yuqin Liu

Abstract read
PubMed Publisher
In one paragraph

Article in Human cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. 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

9 authors.

Fang Cao *Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Pathology, Peking University Cancer Hospital and Institute, Beijing, 100142, People's Republic of China.
Jiayin Dai *Department of Pathology, Cell Resource Center, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) and School of Basic Medicine, Peking Union Medical College (PUMC), Beijing, 100005, People's Republic of China.
Kun DongKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Pathology, Peking University Cancer Hospital and Institute, Beijing, 100142, People's Republic of China.
Zhenli YangDepartment of Pathology, Cell Resource Center, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) and School of Basic Medicine, Peking Union Medical College (PUMC), Beijing, 100005, People's Republic of China.
Yanli ZhuKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Pathology, Peking University Cancer Hospital and Institute, Beijing, 100142, People's Republic of China.
Changsong QiBeijing Key Laboratory of Cell and Gene Therapy for Solid Tumor, State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Early Drug Development Centre, Peking University Cancer Hospital and Institute, Beijing, 100142, People's Republic of China.
Dongmei LinKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Pathology, Peking University Cancer Hospital and Institute, Beijing, 100142, People's Republic of China.
Xiaocui BianDepartment of Pathology, Cell Resource Center, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) and School of Basic Medicine, Peking Union Medical College (PUMC), Beijing, 100005, People's Republic of China. bianxiaocui@ibms.cams.cn.
Yuqin LiuDepartment of Pathology, Cell Resource Center, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) and School of Basic Medicine, Peking Union Medical College (PUMC), Beijing, 100005, People's Republic of China. liuyuqin@pumc.edu.cn.ORCID 0000-0003-3720-4982

Funding

Chinese Academy of Medical Sciences Initiative for Innovative Medicine 2021-I2M-1-053
6 · The paper itself

Abstract

A 62-year-old woman with EGFR exon 19-mutant lung adenocarcinoma developed resistance to osimertinib after 13 months of treatment. At progression, genetic analysis revealed persistence of the EGFR mutation and acquisition of a TPM3-NTRK1 fusion. Cells from the pleural effusion at this stage were cultured and established as a continuous cell line, LUNK1. LUNK1 cells displayed epithelial characteristics, with a population doubling time of 57.66 h in vitro and 100% tumorigenicity in vivo. Xenograft histopathology showed poorly differentiated lung adenocarcinoma exhibiting solid, acinar, and micropapillary patterns. Immunohistochemistry confirmed positivity for CK7, TTF-1, Napsin A, EGFR, and pan-TRK. EGFR exon 19 deletion and TPM3-NTRK1 fusion were confirmed by whole-exome and RNA sequencing, respectively, and further validated by PCR and Sanger sequencing. Drug sensitivity assays revealed an IC₅₀ of 64.0 nM for entrectinib and 806.8 nM for osimertinib, indicating reduced sensitivity to EGFR inhibition. NTRK1 knockdown significantly increased osimertinib sensitivity (124.5-264.5 fold) and reduced entrectinib sensitivity (8.7-19.0 fold), suggesting NTRK1 as a key regulator of drug response. We provided experimental evidence for that TPM3-NTRK1 fusions can mediate acquired resistance to osimertinib in a new lung adenocarcinoma cell line. LUNK1 represents a useful preclinical model for investigating resistance mechanisms and assessing dual-targeted treatment strategies.

Indexed as

AcrylamidesAdenocarcinoma of LungAniline CompoundsAntineoplastic AgentsDrug Resistance, NeoplasmLung NeoplasmsReceptor, trkATropomyosinAnimalsBenzamidesCell Line, TumorErbB ReceptorsFemaleHumansIndolesMiceAcrylamidesAniline CompoundsAntineoplastic AgentsBenzamidesEGFR protein, humanErbB ReceptorsIndolesNTRK1 protein, humanosimertinibPyrimidinesReceptor, trkATPM3 protein, humanTropomyosinContinuous cell lineEGFR-targeted therapyLung adenocarcinomaNTRK gene fusionOsimertinib resistance

Identifiers

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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.