Evidence map›Paper›PMID 36373784›Full record

ArticleThe Journal of pathology2023

Nuclear pCHK1 as a potential biomarker of increased sensitivity to ATR inhibition.

Vignesh Sundararajan, Tuan Zea Tan, Diana Lim, Yanfen Peng, Antje Margret Wengner, Natalie Yan Li Ngoi, Anand D Jeyasekharan, David Shao Peng Tan

Open access · hybridAbstract read
In one paragraph

Article in The Journal of pathology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.6field-weighted citation impact, top 35% 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

6 citing papers in PubMed, 8 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. ALK signaling primes the DNA damage response sensitizing ALK-driven neuroblastoma to therapeutic ATR inhibition.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  6. 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

8 authors at 4 institutions in 2 countries.

Vignesh SundararajanCancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.ORCID 0000-0002-3982-3026
Tuan Zea TanCancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.ORCID 0000-0001-6624-1593
Diana LimDepartment of Pathology, National University Hospital, Singapore, Singapore.
Yanfen PengCancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
Antje Margret WengnerBayer AG, Pharmaceuticals, Berlin, Germany.
Natalie Yan Li NgoiDepartment of Haematology-Oncology, National University Cancer Institute, Singapore, Singapore.
Anand D JeyasekharanCancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
David Shao Peng TanCancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
National University of Singapore · SGBayer (Germany) · DENational University Cancer Institute, Singapore · SGNational University Hospital · SG

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Excessive genomic instability coupled with abnormalities in DNA repair pathways induces high levels of 'replication stress' when cancer cells propagate. Rather than hampering cancer cell proliferation, novel treatment strategies are turning their attention towards targeting cell cycle checkpoint kinases (such as ATR, CHK1, WEE1, and others) along the DNA damage response and replicative stress response pathways, thereby allowing unrepaired DNA damage to be carried forward towards mitotic catastrophe and apoptosis. The selective ATR kinase inhibitor elimusertib (BAY 1895344) has demonstrated preclinical and clinical monotherapy activity; however, reliable predictive biomarkers of treatment benefit are still lacking. In this study, using gene expression profiling of 24 cell lines from different cancer types and in a panel of ovarian cancer cell lines, we found that nuclear-specific enrichment of checkpoint kinase 1 (CHK1) correlated with increased sensitivity to elimusertib. Using an advanced multispectral imaging system in subsequent cell line-derived xenograft specimens, we showed a trend between nuclear phosphorylated CHK1 (pCHK1) staining and increased sensitivity to the ATR inhibitor elimusertib, indicating the potential value of pCHK1 expression as a predictive biomarker of ATR inhibitor sensitivity. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Indexed as

DNA DamageProtein Kinase InhibitorsAtaxia Telangiectasia Mutated ProteinsBiomarkersCell Cycle ProteinsCell LineCell Line, TumorCell ProliferationCheckpoint Kinase 1FemaleHumansAtaxia Telangiectasia Mutated ProteinsATR protein, humanBiomarkersCell Cycle ProteinsCheckpoint Kinase 1Protein Kinase InhibitorsATR inhibitorBAY 1895344biomarkerelimusertibpCHK1replicative stress response

Identifiers

PMID36373784
PMCPMC10107453
OpenAlexW4308956910

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.