Evidence map›Paper›PMID 37979706›Full record

ArticleInternational journal of radiation oncology, biology, physics2024

MET Inhibitor Capmatinib Radiosensitizes MET Exon 14-Mutated and MET-Amplified Non-Small Cell Lung Cancer.

Shrey Ramesh, Ahmet Cifci, Saahil Javeri, Rachel L Minne, Colin A Longhurst, Kwangok P Nickel, Randall J Kimple, Andrew M Baschnagel

Open access · greenAbstract read
In one paragraph

Article in International journal of radiation oncology, biology, physics, 2024. 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
1.2field-weighted citation impact, top 20% of its field
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, 6 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 1 institution in 1 country.

Shrey RameshDepartment of Human Oncology, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin.
Ahmet CifciDepartment of Human Oncology, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin.
Saahil JaveriDepartment of Human Oncology, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin.
Rachel L MinneDepartment of Human Oncology, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin.
Colin A LonghurstDepartment of Biostatistics and Medical Informatics, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin.
Kwangok P NickelDepartment of Human Oncology, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin.
Randall J KimpleDepartment of Human Oncology, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin; University of Wisconsin Carbone Cancer Center, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin. Electronic address: rkimple@humonc.wisc.edu.
Andrew M BaschnagelDepartment of Human Oncology, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin; University of Wisconsin Carbone Cancer Center, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin. Electronic address: baschnagel@humonc.wisc.edu.
University of Wisconsin–Madison · US

Funding

UW COMPREHENSIVE CANCER CENTER SUPPORTP30CA014520 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI Christian Capitini · 1985 to 2026
$142.6M
Improving the translational value of head and neck cancer patient-in-mouse modelsR37CA255330 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI Randall J. Kimple · 2021 to 2026
$3.5M
NCI NIH HHS P30 CA014520NCI NIH HHS R37 CA255330
6 · The paper itself

Abstract

purposeThe objective of this study was to investigate the effects of inhibiting the MET receptor with capmatinib, a potent and clinically relevant ATP-competitive tyrosine kinase inhibitor, in combination with radiation in MET exon 14-mutated and MET-amplified non-small cell lung (NSCLC) cancer models. METHODS AND MATERIALS: In vitro effects of capmatinib and radiation on cell proliferation, colony formation, MET signaling, apoptosis, and DNA damage repair were evaluated. In vivo tumor responses were assessed in cell line xenograft and patient-derived xenograft models. Immunohistochemistry was used to confirm the in vitro results.

resultsIn vitro clonogenic survival assays demonstrated radiosensitization with capmatinib in both MET exon 14-mutated and MET-amplified NSCLC cell lines. No radiation-enhancing effect was observed in MET wild-type NSCLC and a human bronchial epithelial cell line. Minimal apoptosis was detected with the combination of capmatinib and radiation. Capmatinib plus radiation compared with radiation alone resulted in inhibition of DNA double-strand break repair, as measured by prolonged expression of γH2AX. In vivo, the combination of capmatinib and radiation significantly delayed tumor growth compared with vehicle control, capmatinib alone, or radiation alone. Immunohistochemistry indicated inhibition of phospho-MET and phospho-S6 and a decrease in Ki67 with inhibition of MET.

conclusionsInhibition of MET with capmatinib enhances the effect of radiation in both MET exon 14-mutated and MET-amplified NSCLC models.

Indexed as

BenzamidesCarcinoma, Non-Small-Cell LungLung NeoplasmsTriazinesCell Line, TumorExonsHumansImidazolesProtein Kinase InhibitorsProto-Oncogene Proteins c-metBenzamidescapmatinibImidazolesProtein Kinase InhibitorsProto-Oncogene Proteins c-metTriazines

Identifiers

PMID37979706
PMCPMC12121486
OpenAlexW4388736445

What OpenQuestion holds

Textmetadata
LicenceTDM
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 OpenQuestion graph.