Evidence map›Paper›PMID 35159046›Full record

ArticleCancers2022

A Polytherapy Strategy Using Vincristine and ALK Inhibitors to Sensitise EML4-ALK-Positive NSCLC.

Josephina Sampson, Hyun-Min Ju, Ji-Young Song, Andrew M Fry, Richard Bayliss, Jene Choi

Open access · goldAbstract read
In one paragraph

Article in Cancers, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.4field-weighted citation impact, top 19% 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

7 citing papers in PubMed, 9 citations in OpenAlex.

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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

6 authors at 3 institutions in 2 countries.

Josephina SampsonAstbury Centre for Structural Molecular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK.ORCID 0000-0002-0147-6014
Hyun-Min JuDepartment of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, Korea.
Ji-Young SongDepartment of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, Korea.
Andrew M FryDepartment of Molecular and Cell Biology, University of Leicester, Leicester LE1 9HN, UK.
Richard BaylissAstbury Centre for Structural Molecular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK.
Jene ChoiDepartment of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, Korea.
Ulsan College · KRUniversity of Leeds · GBUniversity of Leicester · GB

Funding

Cancer Research UK 23302Cancer Research UK C24461/A23302Medical Research Council MC_PC_17171
6 · The paper itself

Abstract

The oncogenic fusion of EML4-ALK is present in about 4-6% of non-small cell lung cancer (NSCLC). A targeted approach with ALK tyrosine kinase inhibitors (TKIs) has been proven highly effective in ALK-positive NSCLC patients. However, despite the initial responses, the outcome of the treatment is variable. Previous studies have shown that the differential response depends in part on the type of EML4-ALK variant. Here, we examined the combination of ALK inhibitors and microtubule poison, vincristine, in cells expressing EML4-ALK V1 and V3, the two most common variants in NSCLC. We showed that combination therapy of ALK-TKIs with vincristine had anti-proliferative effects and blocked RAS/MAPK, PI3K/AKT and JAK/STAT3 signalling pathways in EML4-ALK V1 but not V3 cells. Our results demonstrate that high levels of tubulin acetylation are associated with poor response to vincristine in EML4-ALK V3 cells. Additionally, we demonstrated differences in microtubule stability between the two EML4-ALK fusions. EML4-ALK V3 cells exhibited dynamic microtubules that confer poor response to vincristine compared to V1 cells. Hence, we suggested that the portion of EML4 in the fusion has an important role for the outcome of the combination treatment.

Indexed as

acetylationALK tyrosine kinase inhibitorscancerEML4-ALKmicrotubulesNSCLCvincristine

Identifiers

PMID35159046
PMCPMC8833940
OpenAlexW4210703811

What OpenQuestion holds

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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 OpenQuestion graph.