Evidence map›Paper›PMID 31795298›Full record

ArticleCells2019

Afatinib Overcomes Pemetrexed-Acquired Resistance in Non-Small Cell Lung Cancer Cells Harboring an EML4-ALK Rearrangement.

Ji-Hyun Kwon, Kui-Jin Kim, Ji Hea Sung, Koung Jin Suh, Ji Yun Lee, Ji-Won Kim, Se Hyun Kim, Jeong-Ok Lee, Jin Won Kim, Yu Jung Kim and 6 more

Open access · goldAbstract read
In one paragraph

Article in Cells, 2019. 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
1.4field-weighted citation impact, top 17% 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

6 citing papers in PubMed, 12 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

16 authors at 2 institutions in 1 country.

Ji-Hyun KwonTranslational Medicine, Department of Medicine, Graduate School, Seoul National University College of Medicine, Seoul 03080, Korea.
Kui-Jin KimBiomedical Research Institute, Seoul National University Bundang Hospital, Seongnam 13620, Korea.
Ji Hea SungDepartment of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 13620, Korea.
Koung Jin SuhDepartment of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 13620, Korea.
Ji Yun LeeDepartment of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 13620, Korea.
Ji-Won KimDepartment of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 13620, Korea.
Se Hyun KimDepartment of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 13620, Korea.
Jeong-Ok LeeDepartment of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 13620, Korea.
Jin Won KimDepartment of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 13620, Korea.
Yu Jung KimDepartment of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 13620, Korea.
Keun-Wook LeeDepartment of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 13620, Korea.
Jee Hyun KimDepartment of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 13620, Korea.
Soo-Mee BangDepartment of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 13620, Korea.
Soyeon KimCancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea.
Sung-Soo YoonDepartment of Internal Medicine, Seoul National University College of Medicine, Seoul 03080, Korea.
Jong Seok LeeTranslational Medicine, Department of Medicine, Graduate School, Seoul National University College of Medicine, Seoul 03080, Korea.
Seoul National University · KRSeoul National University Bundang Hospital · KR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe aim of this study is to elucidate the mechanisms of acquired resistance to pemetrexed in echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) rearranged non-small cell lung cancer.

methodsWe analyzed the sensitivity to pemetrexed and the expression patterns of various proteins after pemetrexed treatment in the cell lines, A549, NCI-H460, NCI-H2228 harboring EML4-ALK variant 3, and NCI-H3122 harboring EML4-ALK variant 1. Pemetrexed-resistant cell lines were also generated through long-term exposure to pemetrexed.

resultsThe EML4-ALK variant 1 rearranged NCI-H3122 was found to be more sensitive than the other cell lines. Cell cycle analysis after pemetrexed treatment showed that the fraction of cells in the S phase increased in A549, NCI-H460, and NCI-H2228, whereas the fraction in the apoptotic sub-G

conclusionThe activation of EGFR-HER2 contributes to the acquisition of resistance to pemetrexed in EML4-ALK rearranged non-small cell lung cancer. However, the inhibition of this alternative survival signaling pathway with RNAi against EGFR-HER2 and with afatinib overcomes this resistance.

Indexed as

Gene RearrangementAfatinibAntineoplastic AgentsApoptosis Regulatory ProteinsCarcinoma, Non-Small-Cell LungCell CycleCell Line, TumorCell ProliferationDrug Resistance, NeoplasmHumansLung NeoplasmsOncogene Proteins, FusionPemetrexedProtein Kinase InhibitorsReceptor Protein-Tyrosine KinasesRNA InterferenceAfatinibAntineoplastic AgentsApoptosis Regulatory ProteinsEML4-ALK fusion protein, humanOncogene Proteins, FusionPemetrexedProtein Kinase InhibitorsReceptor Protein-Tyrosine Kinasesafatinibdrug resistanceEML4-ALK rearrangementlung cancerpemetrexed

Identifiers

PMID31795298
PMCPMC6953071
OpenAlexW2989648331

What OpenQuestion holds

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LicenceCC BY
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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.