Evidence map›Paper›PMID 41436729›Full record

ArticleNature communications2025

Large-scale drug sensitivity, gene dependency, and proteogenomic analyses of telomere maintenance mechanisms in cancer cells.

Yangxiu Wu, Zhaoxiang Cai, Dale Cross, Jane R Noble, Kelsy Prest, Jamie Littleboy, Scott B Cohen, Baylee Edlundh, Jennifer M S Koh, Ran Xu and 12 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. 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

22 authors.

Yangxiu WuCancer Research Unit, Children's Medical Research Institute, Faculty of Medicine and Health, the University of Sydney, Westmead, NSW, Australia.ORCID http://orcid.org/0000-0001-9499-2239
Zhaoxiang CaiProCan®, Children's Medical Research Institute, Faculty of Medicine and Health, the University of Sydney, Westmead, NSW, Australia.ORCID http://orcid.org/0000-0003-3809-0817
Dale CrossCancer Research Unit, Children's Medical Research Institute, Faculty of Medicine and Health, the University of Sydney, Westmead, NSW, Australia.
Jane R NobleCancer Research Unit, Children's Medical Research Institute, Faculty of Medicine and Health, the University of Sydney, Westmead, NSW, Australia.
Kelsy PrestCancer Research Unit, Children's Medical Research Institute, Faculty of Medicine and Health, the University of Sydney, Westmead, NSW, Australia.
Jamie LittleboyCancer Research Unit, Children's Medical Research Institute, Faculty of Medicine and Health, the University of Sydney, Westmead, NSW, Australia.
Scott B CohenCell Biology Unit, Children's Medical Research Institute, Faculty of Medicine and Health, the University of Sydney, Westmead, NSW, Australia.
Baylee EdlundhCancer Research Unit, Children's Medical Research Institute, Faculty of Medicine and Health, the University of Sydney, Westmead, NSW, Australia.
Jennifer M S KohProCan®, Children's Medical Research Institute, Faculty of Medicine and Health, the University of Sydney, Westmead, NSW, Australia.
Ran XuCancer Research Unit, Children's Medical Research Institute, Faculty of Medicine and Health, the University of Sydney, Westmead, NSW, Australia.
Zainab NoorProCan®, Children's Medical Research Institute, Faculty of Medicine and Health, the University of Sydney, Westmead, NSW, Australia.ORCID http://orcid.org/0000-0002-9314-5705
Milad BastamiBioinformatics Unit, Children's Medical Research Institute, Faculty of Medicine and Health, the University of Sydney, Westmead, NSW, Australia.ORCID http://orcid.org/0000-0002-7686-4505
Sara ValentiniWellcome Sanger Institute, Wellcome Genome Campus, Cambridge, UK.
Laura RichardsonWellcome Sanger Institute, Wellcome Genome Campus, Cambridge, UK.ORCID http://orcid.org/0000-0002-8075-3816
Syd BarthorpeWellcome Sanger Institute, Wellcome Genome Campus, Cambridge, UK.
Nader ArymaneshBioinformatics Unit, Children's Medical Research Institute, Faculty of Medicine and Health, the University of Sydney, Westmead, NSW, Australia.
Phillip J RobinsonProCan®, Children's Medical Research Institute, Faculty of Medicine and Health, the University of Sydney, Westmead, NSW, Australia.ORCID http://orcid.org/0000-0002-7878-0313
Peter G HainsProCan®, Children's Medical Research Institute, Faculty of Medicine and Health, the University of Sydney, Westmead, NSW, Australia.ORCID http://orcid.org/0000-0002-7276-1760
Mathew J GarnettWellcome Sanger Institute, Wellcome Genome Campus, Cambridge, UK.ORCID http://orcid.org/0000-0002-2618-4237
Qing ZhongProCan®, Children's Medical Research Institute, Faculty of Medicine and Health, the University of Sydney, Westmead, NSW, Australia. qzhong@cmri.org.au.ORCID http://orcid.org/0000-0002-5340-301X
Roger R ReddelCancer Research Unit, Children's Medical Research Institute, Faculty of Medicine and Health, the University of Sydney, Westmead, NSW, Australia. rreddel@cmri.org.au.ORCID http://orcid.org/0000-0002-6302-6107
Karen L MacKenzieCancer Research Unit, Children's Medical Research Institute, Faculty of Medicine and Health, the University of Sydney, Westmead, NSW, Australia. kmackenzie@cmri.org.au.ORCID http://orcid.org/0000-0003-2996-1617

Funding

Cancer Council NSW (Cancer Council New South Wales) RG24-05Cancer Institute NSW (Cancer Institute New South Wales) 2017/TPG001, REG171150Department of Health | National Health and Medical Research Council (NHMRC) GNT1170739Department of Health | National Health and Medical Research Council (NHMRC) GNT1170739, H2020-SC1-DTH-2018-1National Breast Cancer Foundation (NBCF) IIRS-18-164NSW Ministry of Health (NSW Health) CMP-01Wellcome TrustWellcome Trust 206194
6 · The paper itself

Abstract

Replicative immortality is a hallmark of cancer, driven by the activation of telomere maintenance mechanisms, that is yet to be therapeutically exploited. To expedite discoveries that will enable the development of therapeutics that target telomere maintenance mechanisms, this study provides a resource of telomere biology metrics for a pan-cancer panel of 976 cell lines. We generate proteomic data from data-independent-acquisition mass spectrometry for most of these cell lines and integrate pre-existing multi-omic, drug sensitivity, and molecular dependency data from CRISPR/Cas9 knock-out screens. The data illustrate a broad range and heterogeneity in telomere biology, including states that diverge from the binary model of telomere maintenance activation involving either telomerase or the Alternative Lengthening of Telomeres mechanism. Using the telomere biology metrics and multi-omic data, we derive proteomic and transcriptomic predictors of Alternative Lengthening of Telomeres and telomerase activity levels. Our investigations also reveal molecular vulnerabilities associated with the Alternative Lengthening of Telomeres mechanism and drug sensitivity correlating with telomerase activity levels. These findings illustrate opportunities for leveraging this resource to realize the potential for telomere biology-directed cancer therapeutics and companion diagnostics.

Indexed as

Antineoplastic AgentsNeoplasmsProteogenomicsTelomereTelomere HomeostasisCell Line, TumorCRISPR-Cas SystemsDrug Resistance, NeoplasmHumansProteomicsTelomeraseAntineoplastic AgentsTelomerase

Identifiers

PMID41436729
PMCPMC12727880

What Socratic 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 Socratic graph.