Evidence map›Paper›PMID 40878657›Full record

ArticleMolecular oncology2025

The influence of ROS1 fusion partners and resistance mechanisms in ROS1-TKI-treated non-small cell lung cancer patients.

Fenneke Zwierenga, Christa Dijkhuizen, Patrick Korthuis, Wim Timens, Harry Groen, Jeroen Hiltermann, Anke van den Berg, Lyndsay Drayer, Anthonie van der Wekken

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 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Pharmacogenomics in oncology: mutation-targeted therapy and biomarker integration in non-small cell lung cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Review
  2. Review
  3. Review
  4. Review
  5. Article
  6. 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

9 authors.

Fenneke ZwierengaDepartment of Pulmonary Medicine, University of Groningen, University Medical Center Groningen, The Netherlands.ORCID 0000-0001-8993-0105
Christa DijkhuizenInstitute For Life Science and Technology, Hanze University of Applied Sciences, Groningen, The Netherlands.
Patrick KorthuisInstitute For Life Science and Technology, Hanze University of Applied Sciences, Groningen, The Netherlands.
Wim TimensDepartment of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, The Netherlands.
Harry GroenDepartment of Pulmonary Medicine, University of Groningen, University Medical Center Groningen, The Netherlands.
Jeroen HiltermannDepartment of Pulmonary Medicine, University of Groningen, University Medical Center Groningen, The Netherlands.
Anke van den BergDepartment of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, The Netherlands.
Lyndsay DrayerInstitute For Life Science and Technology, Hanze University of Applied Sciences, Groningen, The Netherlands.
Anthonie van der WekkenDepartment of Pulmonary Medicine, University of Groningen, University Medical Center Groningen, The Netherlands.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Clinical outcomes in ROS1-fusion positive (ROS1+) non-small cell lung cancer (NSCLC) by fusion partner and resistance mechanisms are limited. This cohort study included 56 ROS1+ patients (FISH or NGS confirmed); fusion partners were identified in 27 cases, including CD74 (n = 10), EZR (n = 7), and SDC4 (n = 7). Clinical data were available for 50 patients (median age 62; 51% female; 32% never-smokers). Forty patients received tyrosine kinase inhibitors (TKIs), mostly crizotinib (n = 38). Crizotinib showed a 55% objective response rate (ORR) and a median progression-free survival (mPFS) of 5.3 months. Brain metastases (HR 2.65, 95% CI 1.06-6.60, P = 0.037) and prior chemotherapy (HR 3.17, 95% CI 1.35-7.45, P = 0.008) had a higher risk of progression. Sixteen patients received subsequent lorlatinib, with an ORR of 28% and mPFS of 3.7 months. G2032R and L2026M resistance mutations were identified in four lorlatinib non-responders, and in vitro studies confirmed resistance to lorlatinib. Fusion partners did not affect crizotinib outcomes. Lorlatinib was ineffective against on-target resistance. Real-world data showed lower TKI efficacy than clinical trials, highlighting the role of clinical and molecular factors in treatment response.

Indexed as

Carcinoma, Non-Small-Cell LungDrug Resistance, NeoplasmLung NeoplasmsOncogene Proteins, FusionProtein Kinase InhibitorsProtein-Tyrosine KinasesProto-Oncogene ProteinsAdultAgedAged, 80 and overAminopyridinesAntigens, Differentiation, B-LymphocyteCrizotinibFemaleHistocompatibility Antigens Class IIHumansAminopyridinesAntigens, Differentiation, B-LymphocyteCrizotinibHistocompatibility Antigens Class IIinvariant chainLactamslorlatinibOncogene Proteins, FusionProtein Kinase InhibitorsProtein-Tyrosine KinasesProto-Oncogene ProteinsPyrazolesROS1 protein, humanNon‐small cell lung cancerresistanceROS1

Identifiers

PMID40878657
PMCPMC12591307

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.