Evidence map›Paper›PMID 29300322›Full record

ArticleCancers2018

Mutations in EMT-Related Genes in ALK Positive Crizotinib Resistant Non-Small Cell Lung Cancers.

Jiacong Wei, Anthonie J van der Wekken, Ali Saber, Miente M Terpstra, Ed Schuuring, Wim Timens, T Jeroen N Hiltermann, Harry J M Groen, Anke van den Berg, Klaas Kok

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancers, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
6.4field-weighted citation impact, top 3% 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

20 citing papers in PubMed, 52 citations in OpenAlex.

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  13. Changing ALK-TKI-Resistance Mechanisms in Rebiopsies ofInternational journal of molecular sciences · 2020
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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 at 1 institution in 2 countries.

Jiacong WeiDepartment of Genetics, University of Groningen, University Medical Centre Groningen, 9700 RB Groningen, The Netherlands. weijiacong@126.com.ORCID 0000-0002-6672-7531
Anthonie J van der WekkenDepartment of Pulmonary Diseases, University of Groningen, University Medical Centre Groningen, 9700 RB Groningen, The Netherlands.
Ali SaberDepartment of Pathology and Medical Biology, University of Groningen, University Medical Centre Groningen, 9700 RB Groningen, The Netherlands. a.saber814@gmail.com.ORCID 0000-0002-7110-6860
Miente M TerpstraDepartment of Genetics, University of Groningen, University Medical Centre Groningen, 9700 RB Groningen, The Netherlands. m.m.terpstra.cluster@gmail.com.
Ed SchuuringDepartment of Pathology and Medical Biology, University of Groningen, University Medical Centre Groningen, 9700 RB Groningen, The Netherlands. e.schuuring@umcg.nl.
Wim TimensDepartment of Pathology and Medical Biology, University of Groningen, University Medical Centre Groningen, 9700 RB Groningen, The Netherlands. w.timens@umcg.nl.
T Jeroen N HiltermannDepartment of Pulmonary Diseases, University of Groningen, University Medical Centre Groningen, 9700 RB Groningen, The Netherlands. t.j.n.hiltermann@umcg.nl.
Harry J M GroenDepartment of Pulmonary Diseases, University of Groningen, University Medical Centre Groningen, 9700 RB Groningen, The Netherlands. h.j.m.groen@umcg.nl.
Anke van den BergDepartment of Pathology and Medical Biology, University of Groningen, University Medical Centre Groningen, 9700 RB Groningen, The Netherlands. a.j.van.der.wekken@umcg.nl.
Klaas KokDepartment of Genetics, University of Groningen, University Medical Centre Groningen, 9700 RB Groningen, The Netherlands. k.kok@umcg.nl.
University Medical Center Groningen · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Crizotinib is an effective drug for patients with anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC), but upon treatment, the tumors inevitably become crizotinib resistant in time. The resistance mechanisms are only partly understood. In this study, we aim to identify gene mutations associated with resistance in ALKpositive advanced non-squamous NSCLC treated with crizotinib. Four ALK positive patients with progressive disease following crizotinib treatment were identified with paired pre- and post-crizotinib tumor tissue from our previously published cohort. Somatic variants in these samples were detected by whole exome sequencing. In one of the four patients, an ALK-resistance associated mutation was identified. In the other three patients, no ALK-resistance associated mutations were present. In these patients we identified 89 relevant somatic mutations in 74 genes that were specific to the resistant tumors. These genes were enriched in 15 pathways. Four pathways, were related to epithelial-mesenchymal transition (EMT): proteoglycans in cancer, HIF-1 signaling, FoxO signaling pathway, and ECM-receptor interaction. Analysis of other EMT-related pathways revealed three additional genes with mutations specific to the crizotinib-resistant tumor samples. The enrichment of mutations in genes associated with EMT-related pathways indicates that loss of epithelial differentiation may represent a relevant resistance mechanism for crizotinib.

Indexed as

adenocarcinomaALKcrizotinib resistancewhole exome sequencing

Identifiers

PMID29300322
PMCPMC5789360
OpenAlexW2782175472

What OpenQuestion 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 OpenQuestion graph.