Evidence map›Paper›PMID 30352565›Full record

ArticleBMC cancer2018

Generation and characterization of MEK and ERK inhibitors- resistant non-small-cells-lung-cancer (NSCLC) cells.

Alice Iezzi, Elisa Caiola, Arianna Scagliotti, Massimo Broggini

Open access · goldAbstract read
In one paragraph

Article in BMC cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
0.6field-weighted citation impact, top 33% 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

8 citing papers in PubMed, 10 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

4 authors at 1 institution in 1 country.

Alice IezziLaboratory of Moleular Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.
Elisa CaiolaLaboratory of Moleular Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.
Arianna ScagliottiLaboratory of Moleular Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.
Massimo BrogginiLaboratory of Moleular Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy. massimo.broggini@marionegri.it.ORCID http://orcid.org/0000-0002-8138-9358
Mario Negri Institute for Pharmacological Research · IT

Funding

Associazione Italiana per la Ricerca sul Cancro IG 16792
6 · The paper itself

Abstract

backgroundThe RAS/RAF/MEK/ERK pathway is one of the most downregulated pathway in cancer. Inhibitors of RAF and MEK have established clinical use while ERK inhibitors recently faced the clinic. We aimed to generate resistant cell lines which could be helpful for defining new combinations able to overcome resistance.

methodsthe human NSCLC cell line NCI-H727, sensitive to both MEK and ERK inhibitors, was treated with increasing concentrations of MEK162 (as MEK inhibitor) or SCH772984 as ERK inhibitor.

resultswe successfully obtained a MEK resistant subline (H727/MEK, after 40 passages) as well as an ERK resistant subline (H727/SCH, after 18 passages). The two resistant sublines H727/MEK and H727/SCH were cross-resistant to ERK and MEK inhibitors, respectively, but not to RAF inhibitors. The sublines maintained the responsiveness to inhibitors of the parallel PI3K/akt/mTOR pathway as well as to agents with different mechanism of action. Mechanistically, treatment of sensitive and resistant cells with MEK or ERK inhibitors was able to induce a similar inhibition of ERK phosphorylation, while only in parental cells the drugs were able to induce a downregulation of S6 and RSK phosphorylation.

conclusionsthese resistant cells represent an important tool for further studies on the mechanisms of resistance and ways to overcome it.

Indexed as

Cell Line, TumorDrug Resistance, NeoplasmCarcinoma, Non-Small-Cell LungHumansLung NeoplasmsMAP Kinase Signaling SystemProtein Kinase InhibitorsProtein Kinase InhibitorsDrug resistanceERK inhibitorsMEK inhibitorsNSCLC

Identifiers

PMID30352565
PMCPMC6199806
OpenAlexW2896818550

What OpenQuestion holds

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LicenceCC BY
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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.