Evidence map›Paper›PMID 29992957›Full record

ArticleNature communications2018

Analysis of PARP inhibitor toxicity by multidimensional fluorescence microscopy reveals mechanisms of sensitivity and resistance.

Jone Michelena, Aleksandra Lezaja, Federico Teloni, Thomas Schmid, Ralph Imhof, Matthias Altmeyer

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.

0numbers the graph read from it
0cells of the map it votes in
79citing papers in PubMed
4.6field-weighted citation impact, top 3% 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

79 citing papers in PubMed, 120 citations in OpenAlex.

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19 more citing papers are in PubMed but not listed here.

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 1 institution in 1 country.

Jone MichelenaDepartment of Molecular Mechanisms of Disease, University of Zurich, CH-8057, Zurich, Switzerland.
Aleksandra LezajaDepartment of Molecular Mechanisms of Disease, University of Zurich, CH-8057, Zurich, Switzerland.
Federico TeloniDepartment of Molecular Mechanisms of Disease, University of Zurich, CH-8057, Zurich, Switzerland.
Thomas SchmidDepartment of Molecular Mechanisms of Disease, University of Zurich, CH-8057, Zurich, Switzerland.
Ralph ImhofDepartment of Molecular Mechanisms of Disease, University of Zurich, CH-8057, Zurich, Switzerland.
Matthias AltmeyerDepartment of Molecular Mechanisms of Disease, University of Zurich, CH-8057, Zurich, Switzerland. matthias.altmeyer@uzh.ch.ORCID http://orcid.org/0000-0003-3780-1170
University of Zurich · CH

Funding

EC | European Research Council (ERC) 714326Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation) PP00P3_150690
6 · The paper itself

Abstract

Exploiting the full potential of anti-cancer drugs necessitates a detailed understanding of their cytotoxic effects. While standard omics approaches are limited to cell population averages, emerging single cell techniques currently lack throughput and are not applicable for compound screens. Here, we employed a versatile and sensitive high-content microscopy-based approach to overcome these limitations and quantify multiple parameters of cytotoxicity at the single cell level and in a cell cycle resolved manner. Applied to PARP inhibitors (PARPi) this approach revealed an S-phase-specific DNA damage response after only 15 min, quantitatively differentiated responses to several clinically important PARPi, allowed for cell cycle resolved analyses of PARP trapping, and predicted conditions of PARPi hypersensitivity and resistance. The approach illuminates cellular mechanisms of drug synergism and, through a targeted multivariate screen, could identify a functional interaction between PARPi olaparib and NEDD8/SCF inhibition, which we show is dependent on PARP1 and linked to PARP1 trapping.

Indexed as

Cell CycleCell LineCell Line, TumorCell SurvivalDNA DamageDNA RepairDrug ResistanceHumansMicroscopy, FluorescencePhthalazinesPiperazinesPoly(ADP-ribose) Polymerase InhibitorsPoly(ADP-ribose) PolymerasesRNA InterferenceTime-Lapse ImagingolaparibPhthalazinesPiperazinesPoly(ADP-ribose) Polymerase InhibitorsPoly(ADP-ribose) Polymerases

Identifiers

PMID29992957
PMCPMC6041334
OpenAlexW2873526615

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.