Evidence map›Paper›PMID 38906870›Full record

ArticleNPJ systems biology and applications2024

Network-driven cancer cell avatars for combination discovery and biomarker identification for DNA damage response inhibitors.

Orsolya Papp, Viktória Jordán, Szabolcs Hetey, Róbert Balázs, Valér Kaszás, Árpád Bartha, Nóra N Ordasi, Sebestyén Kamp, Bálint Farkas, Jerome Mettetal and 5 more

Erratum issuedAbstract read
In one paragraph

Article in NPJ systems biology and applications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Review
  2. Leveraging AI for cell biology discovery.Biochemical Society transactions · 2026
    Review
  3. Review
  4. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors.

Orsolya Papp *Turbine Simulated Cell Technologies, Budapest, Hungary.
Viktória Jordán *Turbine Simulated Cell Technologies, Budapest, Hungary.
Szabolcs HeteyTurbine Simulated Cell Technologies, Budapest, Hungary.
Róbert BalázsTurbine Simulated Cell Technologies, Budapest, Hungary.
Valér KaszásTurbine Simulated Cell Technologies, Budapest, Hungary.
Árpád BarthaTurbine Simulated Cell Technologies, Budapest, Hungary.
Nóra N OrdasiTurbine Simulated Cell Technologies, Budapest, Hungary.
Sebestyén KampTurbine Simulated Cell Technologies, Budapest, Hungary.ORCID http://orcid.org/0000-0002-8485-6054
Bálint FarkasTurbine Simulated Cell Technologies, Budapest, Hungary.ORCID http://orcid.org/0009-0005-5645-4612
Jerome MettetalOncology Bioscience, Research and Early Development, Oncology R&D, AstraZeneca, Waltham, MA, USA.
Jonathan R DryEarly Data Science, Oncology Data Science, Oncology R&D, AstraZeneca, Waltham, MA, USA.ORCID http://orcid.org/0000-0002-1640-2616
Duncan YoungSearch and Evaluation, Oncology R&D, AstraZeneca, Cambridge, UK.
Ben SiddersEarly Data Science, Oncology Data Science, Oncology R&D, AstraZeneca, Cambridge, UK.
Krishna C BulusuEarly Data Science, Oncology Data Science, Oncology R&D, AstraZeneca, Cambridge, UK.ORCID http://orcid.org/0000-0002-5092-6640
Daniel V VeresTurbine Simulated Cell Technologies, Budapest, Hungary. daniel.veres@turbine.ai.ORCID http://orcid.org/0000-0002-2968-0666

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Combination therapy is well established as a key intervention strategy for cancer treatment, with the potential to overcome monotherapy resistance and deliver a more durable efficacy. However, given the scale of unexplored potential target space and the resulting combinatorial explosion, identifying efficacious drug combinations is a critical unmet need that is still evolving. In this paper, we demonstrate a network biology-driven, simulation-based solution, the Simulated Cell™. Integration of omics data with a curated signaling network enables the accurate and interpretable prediction of 66,348 combination-cell line pairs obtained from a large-scale combinatorial drug sensitivity screen of 684 combinations across 97 cancer cell lines (BAC = 0.62, AUC = 0.7). We highlight drug combination pairs that interact with DNA Damage Response pathways and are predicted to be synergistic, and deep network insight to identify biomarkers driving combination synergy. We demonstrate that the cancer cell 'avatars' capture the biological complexity of their in vitro counterparts, enabling the identification of pathway-level mechanisms of combination benefit to guide clinical translatability.

Indexed as

DNA DamageNeoplasmsAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorCell Line, TumorComputer SimulationDrug DiscoveryDrug SynergismHumansSignal TransductionSystems BiologyAntineoplastic AgentsBiomarkers, Tumor

Identifiers

PMID38906870
PMCPMC11192759

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Registered trials

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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.