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Record W4410421452 · doi:10.1016/j.drudis.2025.104381

Synergism or mirage: Current progress and an empirical approach for elucidating combination drug effects

2025· review· en· W4410421452 on OpenAlexafffund
Paola Vottero, Jack A. Tuszyński, Yun K. Tam, Chih‐Yuan Tseng

Bibliographic record

VenueDrug Discovery Today · 2025
Typereview
Languageen
FieldComputer Science
TopicComputational Drug Discovery Methods
Canadian institutionsSinai Health SystemPCL Construction (Canada)University of Alberta
FundersAlliance de recherche numérique du CanadaMitacs
KeywordsDrugDrug discoveryCurrent (fluid)Pharmaceutical sciencesBiochemical engineeringPharmacologyComputational biologyChemistryData scienceRisk analysis (engineering)Computer scienceMedicineBiologyEngineeringBiochemistry

Abstract

fetched live from OpenAlex

In the context of the multitarget paradigm, fixed-dose combination (FDC) drugs, that is, compounds that synergistically target multiple sites when combined, have gained attention for treating complex diseases like cancers and viral infections, as traditional single-drug approaches are often inadequate. This review examines current methods for evaluating and predicting drug synergism in advancing combination drug discovery, highlighting their limitations and providing a unified mathematical framework. Additionally, we present a novel solution to resolve these limitations and improve synergism evaluation, demonstrated through a case study with 20 pairs of FDA-approved chemotherapy drugs for colorectal cancer.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.005
metaresearch head score (Gemma)0.010
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.005
Threshold uncertainty score0.026

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0050.010
Meta-epidemiology (narrow)0.0020.001
Meta-epidemiology (broad)0.0030.002
Bibliometrics0.0030.003
Science and technology studies0.0000.002
Scholarly communication0.0020.003
Open science0.0020.001
Research integrity0.0010.002
Insufficient payload (model declined to judge)0.0050.001

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.047
GPT teacher head0.416
Teacher spread0.369 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designNot applicable
Domainnot available
GenreReview

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations8
Published2025
Admission routes2
Has abstractyes

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