Evidence map›Paper›PMID 28766886›Full record

ArticleCancer medicine2017

Small cell lung carcinoma cell line screen of etoposide/carboplatin plus a third agent.

Beverly A Teicher, Thomas Silvers, Michael Selby, Rene Delosh, Julie Laudeman, Chad Ogle, Russell Reinhart, Ralph Parchment, Julia Krushkal, Dmitriy Sonkin and 3 more

Open access · goldAbstract read
In one paragraph

Article in Cancer medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.2field-weighted citation impact, top 21% 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

13 citing papers in PubMed, 21 citations in OpenAlex.

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  9. New Approaches to SCLC Therapy: From the Laboratory to the Clinic.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2020
    Review
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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

13 authors at 3 institutions in 2 countries.

Beverly A TeicherDevelopmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, Maryland, 20892.ORCID http://orcid.org/0000-0003-1535-7304
Thomas SilversMolecular Pharmacology Group, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, 21702.
Michael SelbyMolecular Pharmacology Group, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, 21702.
Rene DeloshMolecular Pharmacology Group, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, 21702.
Julie LaudemanMolecular Pharmacology Group, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, 21702.
Chad OgleMolecular Pharmacology Group, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, 21702.
Russell ReinhartMolecular Pharmacology Group, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, 21702.
Ralph ParchmentMolecular Pharmacology Group, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, 21702.
Julia KrushkalBiometric Research Program, Division of Cancer Treatment and Diagnosis, Bethesda, Maryland, 20892.
Dmitriy SonkinBiometric Research Program, Division of Cancer Treatment and Diagnosis, Bethesda, Maryland, 20892.
Larry RubinsteinBiometric Research Program, Division of Cancer Treatment and Diagnosis, Bethesda, Maryland, 20892.
Joel MorrisDevelopmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, Maryland, 20892.
David EvansMolecular Pharmacology Group, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, 21702.
Leidos (United States) · USNational Cancer Institute · USNational Cancer Institute · MY

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The SCLC combination screen examined a 9-point concentration response of 180 third agents, alone and in combination with etoposide/carboplatin. The predominant effect of adding a third agent to etoposide/carboplatin was additivity. Less than additive effects occurred frequently in SCLC lines sensitive to etoposide/carboplatin. In SCLC lines with little or no response to etoposide/carboplatin, greater than additive SCLC killing occurred over the entire spectrum of SCLC lines but never occurred in all SCLC lines. Exposing SCLC lines to tubulin-targeted agents (paclitaxel or vinorelbine) simultaneously with etoposide/carboplatin resulted primarily in less than additive cell killing. As single agents, nuclear kinase inhibitors including Aurora kinase inhibitors, Kinesin Spindle Protein/EG5 inhibitors, and Polo-like kinase-1 inhibitors were potent cytotoxic agents in SCLC lines; however, simultaneous exposure of the SCLC lines to these agents along with etoposide/carboplatin, generally, resulted in less than additive cell killing. Several classes of agents enhanced the cytotoxicity of etoposide/carboplatin toward the SCLC lines. Exposure of the SCLC lines to the MDM2 inhibitor JNJ-27291199 produced enhanced killing in 80% of the SCLC lines. Chk-1 inhibitors such as rabusertib increased the cytotoxicity of etoposide/carboplatin to the SCLC lines in an additive to greater than additive manner. The combination of GSK-3β inhibitor LY-2090314 with etoposide/carboplatin increased killing in approximately 40% of the SCLC lines. Exposure to the BET bromodomain inhibitor MK-8628 increased the SCLC cell killing by etoposide/carboplatin in 20-25% of the SCLC lines. Only 10-15% of the SCLC lines had an increased response to etoposide/carboplatin when simultaneously exposed to the PARP inhibitor talazoparib.

Indexed as

Drug Screening Assays, AntitumorAntineoplastic AgentsCarboplatinCell Line, TumorComputational BiologyDose-Response Relationship, DrugDrug SynergismEtoposideGene Expression ProfilingGene Expression Regulation, NeoplasticHumansLung NeoplasmsSmall Cell Lung CarcinomaSmall Molecule LibrariesAntineoplastic AgentsCarboplatinEtoposideSmall Molecule LibrariesSCLCSCLC cell-based screenSCLC combination screenSmall cell lung cancer

Identifiers

PMID28766886
PMCPMC5548882
OpenAlexW2741829550

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.