Evidence map›Paper›PMID 40301300›Full record

ArticleNature communications2025

AI-driven discovery of synergistic drug combinations against pancreatic cancer.

Mohsen Pourmousa, Sankalp Jain, Elena Barnaeva, Wengong Jin, Joshua Hochuli, Zina Itkin, Travis Maxfield, Cleber Melo-Filho, Andrew Thieme, Kelli Wilson and 9 more

Abstract read
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 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing 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

15 citing papers in PubMed.

  1. Review
  2. Unravelling the pathogenesis and therapeutic approaches of pancreatic ductal adenocarcinoma.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Review
  3. Article
  4. Review
  5. Review
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  8. Target discovery and drug design in the era of artificial intelligence.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026
    Review
  9. Medea: An omics AI agent for therapeutic discovery.bioRxiv : the preprint server for biology · 2026
    Article
  10. Review
  11. Review
  12. Article
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  15. 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

19 authors.

Mohsen Pourmousa *National Center for Advancing Translational Sciences (NCATS), National Institutes of Health, 9800 Medical Center Drive, Rockville, MD, 20850, USA.
Sankalp Jain *National Center for Advancing Translational Sciences (NCATS), National Institutes of Health, 9800 Medical Center Drive, Rockville, MD, 20850, USA.
Elena BarnaevaNational Center for Advancing Translational Sciences (NCATS), National Institutes of Health, 9800 Medical Center Drive, Rockville, MD, 20850, USA.
Wengong JinComputer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.ORCID http://orcid.org/0000-0002-0555-3056
Joshua HochuliLaboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, 27599, USA.
Zina ItkinNational Center for Advancing Translational Sciences (NCATS), National Institutes of Health, 9800 Medical Center Drive, Rockville, MD, 20850, USA.
Travis MaxfieldLaboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, 27599, USA.
Cleber Melo-FilhoLaboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, 27599, USA.ORCID http://orcid.org/0000-0003-0056-6971
Andrew ThiemeLaboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, 27599, USA.
Kelli WilsonNational Center for Advancing Translational Sciences (NCATS), National Institutes of Health, 9800 Medical Center Drive, Rockville, MD, 20850, USA.ORCID http://orcid.org/0000-0003-2636-2766
Carleen Klumpp-ThomasNational Center for Advancing Translational Sciences (NCATS), National Institutes of Health, 9800 Medical Center Drive, Rockville, MD, 20850, USA.ORCID http://orcid.org/0000-0002-6646-6132
Sam MichaelNational Center for Advancing Translational Sciences (NCATS), National Institutes of Health, 9800 Medical Center Drive, Rockville, MD, 20850, USA.ORCID http://orcid.org/0000-0002-1070-6563
Noel SouthallNational Center for Advancing Translational Sciences (NCATS), National Institutes of Health, 9800 Medical Center Drive, Rockville, MD, 20850, USA.ORCID http://orcid.org/0000-0003-4500-880X
Tommi JaakkolaComputer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.ORCID http://orcid.org/0000-0002-2199-0379
Eugene N MuratovLaboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, 27599, USA.ORCID http://orcid.org/0000-0003-4616-7036
Regina BarzilayComputer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
Alexander TropshaLaboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, 27599, USA.ORCID http://orcid.org/0000-0003-3802-8896
Marc FerrerNational Center for Advancing Translational Sciences (NCATS), National Institutes of Health, 9800 Medical Center Drive, Rockville, MD, 20850, USA.ORCID http://orcid.org/0000-0003-4569-9137
Alexey V ZakharovNational Center for Advancing Translational Sciences (NCATS), National Institutes of Health, 9800 Medical Center Drive, Rockville, MD, 20850, USA. alexey.zakharov@nih.gov.ORCID http://orcid.org/0000-0003-2466-1711

Funding

Supporting Biomedical Discovery with the ROBOKOP Graph Knowledgebase.U24ES035214 · NIEHS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Christopher Bizon, Alexander Tropsha · 2022 to 2026
$4.0M
Artificial Intelligence Toolkit for Predicting Mixture ToxicityR41ES033857 · NIEHS · PREDICTIVE, LLC · PI TROPSHA, ALEXANDER · 2022 to 2022
$256k
NIEHS NIH HHS R41 ES033857NIEHS NIH HHS U24 ES035214
6 · The paper itself

Abstract

Pancreatic cancer treatment often relies on multi-drug regimens, but optimal combinations remain elusive. This study evaluates predictive approaches to identify synergistic drug combinations using a dataset from the National Center for Advancing Translational Sciences (NCATS). Screening 496 combinations of 32 anticancer compounds against the PANC-1 cells experimentally determined the degree of synergism and antagonism. Three research groups (NCATS, University of North Carolina, and Massachusetts Institute of Technology) leverage these data to apply machine learning (ML) approaches, predicting synergy across 1.6 million combinations. Of the 88 tested, 51 show synergy, with graph convolutional networks achieving the best hit rate and random forest the highest precision. Beyond highlighting the potential of ML, this work delivers 307 experimentally validated synergistic combinations, demonstrating its practical impact in treating pancreatic cancer.

Indexed as

Antineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsDrug DiscoveryPancreatic NeoplasmsCell Line, TumorDrug Screening Assays, AntitumorDrug SynergismHumansMachine LearningAntineoplastic Agents

Identifiers

PMID40301300
PMCPMC12041571

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.