Evidence map›Paper›PMID 41053076›Full record

ArticleNPJ systems biology and applications2025

Constraint based modeling of drug induced metabolic changes in a cancer cell line.

Xavier Benedicto, Åsmund Flobak, Miguel Ponce-de-Leon, Alfonso Valencia

Abstract read
In one paragraph

Article in NPJ systems biology and applications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. 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

4 authors.

Xavier BenedictoBarcelona Supercomputing Center (BSC), Barcelona, Spain.ORCID http://orcid.org/0009-0001-9112-373X
Åsmund FlobakNorwegian University of Science and Technology (NTNU), Trondheim, Norway.ORCID http://orcid.org/0000-0002-3357-425X
Miguel Ponce-de-LeonBarcelona Supercomputing Center (BSC), Barcelona, Spain. miguel.ponce@bsc.es.ORCID http://orcid.org/0000-0002-7496-844X
Alfonso ValenciaBarcelona Supercomputing Center (BSC), Barcelona, Spain.ORCID http://orcid.org/0000-0002-8937-6789

Funding

Horizon 2020 Framework Programme 825070
6 · The paper itself

Abstract

Cancer cells frequently reprogramme their metabolism to support growth and survival, making metabolic pathways attractive targets for therapy. In this study, we investigated the metabolic effects of three kinase inhibitors and their synergistic combinations in the gastric cancer cell line AGS using genome-scale metabolic models and transcriptomic profiling. We applied the tasks inferred from the differential expression (TIDE) algorithm to infer pathway activity changes in the different conditions. We also explored a variant of TIDE that uses task-essential genes to infer metabolic task changes, providing a complementary perspective to the original algorithm. Our results revealed widespread down-regulation of biosynthetic pathways, particularly in amino acid and nucleotide metabolism. Combinatorial treatments induced condition-specific metabolic alterations, including strong synergistic effects in the PI3Ki-MEKi condition affecting ornithine and polyamine biosynthesis. These metabolic shifts provide insight into drug synergy mechanisms and highlight potential therapeutic vulnerabilities. To support reproducibility, we developed an open-source Python package, MTEApy, implementing both TIDE frameworks.

Indexed as

Antineoplastic AgentsNeoplasmsStomach NeoplasmsAlgorithmsCell Line, TumorComputational BiologyDrug SynergismGene Expression ProfilingGene Expression Regulation, NeoplasticHumansMetabolic Networks and PathwaysModels, BiologicalProtein Kinase InhibitorsAntineoplastic AgentsProtein Kinase Inhibitors

Identifiers

PMID41053076
PMCPMC12501097

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.