Evidence map›Paper›PMID 31703356›Full record

ArticleCancers2019

WEE1 Inhibition Enhances Anti-Apoptotic Dependency as a Result of Premature Mitotic Entry and DNA Damage.

Mathilde Rikje Willemijn de Jong, Myra Langendonk, Bart Reitsma, Pien Herbers, Marcel Nijland, Gerwin Huls, Anke van den Berg, Emanuele Ammatuna, Lydia Visser, Tom van Meerten

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

Article in Cancers, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
0.9field-weighted citation impact, top 27% 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

14 citing papers in PubMed, 27 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Review
  7. Article
  8. Using graph-based model to identify cell specific synthetic lethal effects.Computational and structural biotechnology journal · 2023
    Article
  9. Targeting replication stress in cancer therapy.Nature reviews. Drug discovery · 2023
    Review
  10. Review
  11. Article
  12. Review
  13. Pharmacological Inhibition of WEE1 Potentiates the Antitumoral Effect of theInternational journal of molecular sciences · 2020
    Article
  14. Review
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

10 authors at 1 institution in 1 country.

Mathilde Rikje Willemijn de JongDepartment of Hematology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, the Netherlands.
Myra LangendonkDepartment of Hematology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, the Netherlands.
Bart ReitsmaDepartment of Hematology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, the Netherlands.
Pien HerbersDepartment of Hematology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, the Netherlands.
Marcel NijlandDepartment of Hematology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, the Netherlands.ORCID 0000-0002-2740-2873
Gerwin HulsDepartment of Hematology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, the Netherlands.
Anke van den BergDepartment of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, the Netherlands.ORCID 0000-0002-8894-2638
Emanuele AmmatunaDepartment of Hematology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, the Netherlands.
Lydia VisserDepartment of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, the Netherlands.
Tom van MeertenDepartment of Hematology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, the Netherlands.
University Medical Center Groningen · NL

Funding

KWF Kankerbestrijding Mandema StipendiumKWF Kankerbestrijding RUG 2014-6727
6 · The paper itself

Abstract

Genomically unstable cancers are dependent on specific cell cycle checkpoints to maintain viability and prevent apoptosis. The cell cycle checkpoint protein WEE1 is highly expressed in genomically unstable cancers, including diffuse large B-cell lymphoma (DLBCL). Although WEE1 inhibition effectively induces apoptosis in cancer cells, the effect of WEE1 inhibition on anti-apoptotic dependency is not well understood. We show that inhibition of WEE1 by AZD1775 induces DNA damage and pre-mitotic entry in DLBCL, thereby enhancing dependency on BCL-2 and/or MCL-1. Combining AZD1775 with anti-apoptotic inhibitors such as venetoclax (BCL-2i) or S63845 (MCL-1i) enhanced sensitivity in a cell-specific manner. In addition, we demonstrate that both G2/M cell cycle arrest and DNA damage induction put a similar stress on DLBCL cells, thereby enhancing anti-apoptotic dependency. Therefore, genotoxic or cell cycle disrupting agents combined with specific anti-apoptotic inhibitors may be very effective in genomic unstable cancers such as DLBCL and therefore warrants further clinical evaluation.

Indexed as

AZD1775BH3 profilingdiffuse large B-cell lymphomanavitoclaxvenetoclaxWEE1

Identifiers

PMID31703356
PMCPMC6895818
OpenAlexW2988043926

What OpenQuestion holds

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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.