Evidence map›Paper›PMID 27517323›Full record

ArticleOncotarget2016

ABCB1 as predominant resistance mechanism in cells with acquired SNS-032 resistance.

Nadine Löschmann, Martin Michaelis, Florian Rothweiler, Yvonne Voges, Barbora Balónová, Barry A Blight, Jindrich Cinatl

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

Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.4field-weighted citation impact, top 31% 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

4 citing papers in PubMed, 7 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Cyclin-dependent kinase 9 (CDK9) is a novel prognostic marker and therapeutic target in ovarian cancer.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019
    Article
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

7 authors at 2 institutions in 2 countries.

Nadine LöschmannInstitut für Medizinische Virologie, Klinikum der Goethe-Universität, 60596 Frankfurt am Main, Germany.
Martin MichaelisCentre for Molecular Processing and School of Biosciences, University of Kent, Canterbury, UK.
Florian RothweilerInstitut für Medizinische Virologie, Klinikum der Goethe-Universität, 60596 Frankfurt am Main, Germany.
Yvonne VogesInstitut für Medizinische Virologie, Klinikum der Goethe-Universität, 60596 Frankfurt am Main, Germany.
Barbora BalónováSchool of Physical Sciences, University of Kent, Canterbury, UK.
Barry A BlightSchool of Physical Sciences, University of Kent, Canterbury, UK.
Jindrich CinatlInstitut für Medizinische Virologie, Klinikum der Goethe-Universität, 60596 Frankfurt am Main, Germany.
Goethe University Frankfurt · DEUniversity of Kent · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The CDK inhibitor SNS-032 had previously exerted promising anti-neuroblastoma activity via CDK7 and 9 inhibition. ABCB1 expression was identified as major determinant of SNS-032 resistance. Here, we investigated the role of ABCB1 in acquired SNS-032 resistance. In contrast to ABCB1-expressing UKF-NB-3 sub-lines resistant to other ABCB1 substrates, SNS-032-adapted UKF-NB-3 (UKF-NB-3rSNS- 032300nM) cells remained sensitive to the non-ABCB1 substrate cisplatin and were completely re-sensitized to cytotoxic ABCB1 substrates by ABCB1 inhibition. Moreover, UKF-NB-3rSNS-032300nM cells remained similarly sensitive to CDK7 and 9 inhibition as UKF-NB-3 cells. In contrast, SHEPrSNS-0322000nM, the SNS-032-resistant sub-line of the neuroblastoma cell line SHEP, displayed low level SNS-032 resistance also when ABCB1 was inhibited. This discrepancy may be explained by the higher SNS-032 concentrations that were used to establish SHEPrSNS-0322000nM cells, since SHEP cells intrinsically express ABCB1 and are less sensitive to SNS-032 (IC50 912 nM) than UKF-NB-3 cells (IC50 153 nM). In conclusion, we show that ABCB1 expression represents the primary (sometimes exclusive) resistance mechanism in neuroblastoma cells with acquired resistance to SNS-032. Thus, ABCB1 inhibitors may increase the SNS-032 efficacy in ABCB1-expressing cells and prolong or avoid resistance formation.

Indexed as

Drug Resistance, NeoplasmAntineoplastic AgentsATP-Binding Cassette, Sub-Family C ProteinsATP Binding Cassette Transporter, Subfamily BATP Binding Cassette Transporter, Subfamily G, Member 2Cell Line, TumorCyclin-Dependent Kinase 2Cyclin-Dependent Kinase 9Cyclin-Dependent Kinase-Activating KinaseCyclin-Dependent KinasesHumansInhibitory Concentration 50Neoplasm ProteinsNeuroblastomaOxazolesProtein Kinase Inhibitors3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamideABCB1 protein, humanABCG2 protein, humanAntineoplastic AgentsATP-Binding Cassette, Sub-Family C ProteinsATP Binding Cassette Transporter, Subfamily BATP Binding Cassette Transporter, Subfamily G, Member 2BS-181CDK2 protein, humanCDK7 protein, humanCDK9 protein, humanCyclin-Dependent Kinase 2Cyclin-Dependent Kinase 9Cyclin-Dependent Kinase-Activating KinaseCyclin-Dependent Kinasesmultidrug resistance-associated protein 1N-(5-(((5-(1,1-dimethylethyl)-2-oxazolyl)methyl)thio)-2-thiazolyl)-4-piperidinecarboxamideNeoplasm ProteinsOxazolesProtein Kinase InhibitorsPyrazolesPyrimidinesRNA, Small InterferingSulfonamidesThiazolesABCB1cancerCDK inhibitormulti-drug resistanceneuroblastoma

Identifiers

PMID27517323
PMCPMC5295411
OpenAlexW2518301625

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.