Evidence map›Paper›PMID 40168046›Full record

ArticleMolecular oncology2025

MET and NF2 alterations confer primary and early resistance to first-line alectinib treatment in ALK-positive non-small-cell lung cancer.

Jie Hu, Ning Ding, Xiaobo Xu, Yedan Chen, Yong Zhang, Jingwen Liu, Jiebai Zhou, Hairong Bao, Donghui Zhang, Yijun Song and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Review
  2. ALK-tyrosine kinase inhibitor resistance due to acquiredTranslational lung cancer research · 2026
    Article
  3. Article
  4. 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

12 authors.

Jie HuDepartment of Pulmonary Medicine, Shanghai Geriatric Medical Center, China.ORCID 0009-0001-5858-6169
Ning DingDepartment of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.
Xiaobo XuDepartment of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.
Yedan ChenGeneseeq Research Institute, Nanjing Geneseeq Technology Inc., China.ORCID 0000-0002-7942-5540
Yong ZhangDepartment of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.
Jingwen LiuGeneseeq Research Institute, Nanjing Geneseeq Technology Inc., China.
Jiebai ZhouDepartment of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.
Hairong BaoGeneseeq Research Institute, Nanjing Geneseeq Technology Inc., China.
Donghui ZhangDepartment of Pulmonary Medicine, Shanghai Geriatric Medical Center, China.
Yijun SongDepartment of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.
Yang ShaoGeneseeq Research Institute, Nanjing Geneseeq Technology Inc., China.
Yuanlin SongDepartment of Pulmonary Medicine, Shanghai Geriatric Medical Center, China.

Funding

National Key R&D Plan 2020YFC2003700National Natural Science Foundation of China 82070045National Natural Science Foundation of China 82130001Science and Technology Commission of Shanghai Municipality 20DZ2261200Science and Technology Commission of Shanghai Municipality 20XD1401200Science and Technology Commission of Shanghai Municipality 20Z11901000Shanghai Municipal Key Clinical Specialty shslczdzk02201Shanghai Municipal Science and Technology Major Project, Clinical Research Plan of SHDC SHDC2020CR5010-002
6 · The paper itself

Abstract

Although first-line alectinib has prolonged survival in ALK-mutated non-small-cell lung cancers (NSCLCs), the response to treatment varies among patients, and the primary/early development of alectinib resistance mechanisms is still not fully understood. Here, we analyzed molecular profiles of 108 alectinib-treated patients (first-line and second-line after crizotinib) with confirmed relapse by targeted sequencing of cancer-related genes. After first-line treatment, off-target MET and NF2 alterations were more frequent than on-target alterations within the first 6 months, causing primary or early resistance. Conversely, on-target alterations became prevalent after 1 year of first-line alectinib treatment and predominantly after second-line. The incidence of acquired resistance also depended on EML4-ALK variants. In variant 1 (v1), off-target alterations were responsible for 50% of resistance cases after first-line alectinib therapy, whereas on-target mutations had no contribution in this subgroup. In variant 3 (v3), on-target alterations resulted in 46% of resistance cases, whereas only 18% were caused by off-target mutations. After second-line treatment, the most common mutations in v1 were L1196M (42%) and G1269A (25%), while G1202R was detected in 45% of v3 tumors. These findings emphasize the importance of stratifying resistance mechanisms to guide tailored treatment for ALK-positive NSCLCs.

Indexed as

Anaplastic Lymphoma KinaseCarbazolesCarcinoma, Non-Small-Cell LungDrug Resistance, NeoplasmLung NeoplasmsPiperidinesAdultAgedFemaleHumansMaleMiddle AgedMutationNeurofibromin 2Protein Kinase InhibitorsalectinibALK protein, humanAnaplastic Lymphoma KinaseCarbazolesNeurofibromin 2NF2 protein, humanPiperidinesProtein Kinase Inhibitorsalectinib resistanceALK‐rearranged NSCLCEML4‐ALK variantsMETNF2

Identifiers

PMID40168046
PMCPMC12420365

What Socratic holds

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LicenceCC BY
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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 Socratic graph.