Evidence map›Paper›PMID 40227636›Full record

ArticleCancers2025

Presence of On-Target Resistant Mutation in Pre-Treatment Samples of ALK Fusion Gene Positive Lung Cancer Patients.

Weiting Li, Fenneke Zwierenga, Katarina D Andini, Justyna M Bucher, Frank Scherpen, T Jeroen N Hiltermann, Harry J M Groen, Anthonie J van der Wekken, Klaas Kok, Anke van den Berg

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In one paragraph

Article in Cancers, 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. Review
  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

10 authors.

Weiting LiDepartment of Pathology and Medical Biology, University of Groningen, University Medical Centre Groningen, 9713 GZ Groningen, The Netherlands.ORCID 0000-0003-1789-1498
Fenneke ZwierengaDepartment of Pulmonary Diseases, University of Groningen, University Medical Centre Groningen, 9713 GZ Groningen, The Netherlands.
Katarina D AndiniDepartment of Genetics, University of Groningen, University Medical Centre Groningen, 9700 RB Groningen, The Netherlands.ORCID 0000-0003-1541-0128
Justyna M BucherDepartment of Genetics, University of Groningen, University Medical Centre Groningen, 9700 RB Groningen, The Netherlands.
Frank ScherpenDepartment of Pathology and Medical Biology, University of Groningen, University Medical Centre Groningen, 9713 GZ Groningen, The Netherlands.
T Jeroen N HiltermannDepartment of Pulmonary Diseases, University of Groningen, University Medical Centre Groningen, 9713 GZ Groningen, The Netherlands.ORCID 0000-0002-0665-2160
Harry J M GroenDepartment of Pulmonary Diseases, University of Groningen, University Medical Centre Groningen, 9713 GZ Groningen, The Netherlands.ORCID 0000-0002-2978-5265
Anthonie J van der WekkenDepartment of Pulmonary Diseases, University of Groningen, University Medical Centre Groningen, 9713 GZ Groningen, The Netherlands.ORCID 0000-0001-7175-0026
Klaas KokDepartment of Genetics, University of Groningen, University Medical Centre Groningen, 9700 RB Groningen, The Netherlands.ORCID 0000-0001-8655-3439
Anke van den BergDepartment of Pathology and Medical Biology, University of Groningen, University Medical Centre Groningen, 9713 GZ Groningen, The Netherlands.ORCID 0000-0002-8894-2638

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

A subset of ALK+ non-small cell lung cancer (NSCLC) patients relapse on ALK inhibitor (ALKi) treatment due to on-target resistance mutations affecting the tyrosine kinase domain.

objectiveIn this study, we investigated the presence of minor resistant clones in pre-treatment tissue samples and assessed their predictive value for subsequent resistance mechanisms.

methodsUsing the highly sensitive digital droplet (dd)PCR technique, we analyzed 40 tissue samples obtained from 17 patients who had developed on-target resistance mutations after receiving ALKi between 2013 and 2022. We focused on 10 on-target ALKi resistant mutations identified in our patient cohort.

resultsFifteen ALKi resistance mutations were detected in 13 samples from 11/17 patients. Among these, four mutations were observed as resistance mutations in follow-up biopsies taken after first or subsequent lines of ALKi. Comparison of the test results from two subsequent biopsies, before and directly after therapy, revealed presence of the resistance mutation identified upon relapse in the pre-treatment sample of three cases that were all taken from the same tumor location. In six cases taken from different tumor locations, the resistant mutations were not found in the pre-treatment sample.

conclusionsBy using the highly sensitive ddPCR approach, we detected minor clones with on-target resistant mutations in both treatment-naive and relapse biopsies from ALK-positive NSCLC patients. The predictive value of these mutations as the potential resistance-causing mechanism was limited to relapses occurring at the same tumor location as the pre-treatment sample.

Indexed as

ALKddPCRmutationNSCLCresistance

Identifiers

PMID40227636
PMCPMC11987820

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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.