ArticleNature cancer2023
Additivity predicts the efficacy of most approved combination therapies for advanced cancer.
Article in Nature cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.
- Risk-Benefit of Phase 2 Monotherapy Trials in Adult Solid Cancers: A Systematic Review and Meta-Analysis.International journal of cancer · 2026Pooled it
- Panitumumab-Based EGFR Blockade in SMARCB1-Deficient Renal Medullary Carcinoma: Preclinical Basis and Prospective Clinical Activity.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- A novel combination therapy for ER+ breast cancer suppresses drug resistance via an evolutionary double-bind.Molecular systems biology · 2026Article
- Additivity, Not Synergy, Underlies the Efficacy of Current Combination Regimens in Urothelial Cancer.Cancer research communications · 2026Article
- Rethinking the role of synergy calculations in the next century of drug combination discovery.Med (New York, N.Y.) · 2026Review
- Clinical Development of Novel-Novel Multi-Company Combination Therapies in Oncology.Current oncology reports · 2026Review
- Antibiotic-phytochemical combinations against Enterococcus faecalis: a therapeutic strategy optimized using response surface methodology.Antonie van Leeuwenhoek · 2026Article
- Characterizing clinical toxicity in cancer combination therapies.Bioinformatics (Oxford, England) · 2026Article
- Characterization of the anticancer effect of mebendazole and its interaction with standard cytotoxic drugs in patient tumor cellsOncology reports · 2026Article
- Mathematical Oncology: How Modeling Is Transforming Clinical Decision-Making.Cancer research · 2025Review
- A human metabolic map of pharmacological perturbations reveals drug modes of action.Nature biotechnology · 2025Article
- Improved analysis of in vivo drug combination experiments with a comprehensive statistical framework and web-tool.Nature communications · 2025Article
- Biodegradable nanofibrous scaffolds enhance standard of care for glioblastoma via localized targeted therapy.Journal of controlled release : official journal of the Controlled Release Society · 2025Article
- Combination of the Novel RAF Dimer Inhibitor Brimarafenib With the MEK Inhibitor Mirdametinib Is Effective Against NRAS Mutant Melanoma.Pigment cell & melanoma research · 2025Article
- Discovering anticancer drug target combinations via network-informed signaling-based approach.Communications medicine · 2025Article
- Rational Design of Non-Toxic Multidrug Combinations Demonstrates Durable and Hypoxia-Enhanced Efficacy Against Renal Cell Carcinoma.Pharmaceutics · 2025Article
- Article
- Targeted ferroptosis induction enhances chemotherapy efficacy in chemoresistant neuroblastoma.NPJ precision oncology · 2025Article
- Multi-drug pharmacotyping improves therapy prediction in pancreatic cancer organoids.Cancer cell international · 2025Article
- Personalizing chemotherapy drug selection using a novel transcriptomic chemogram.PLoS computational biology · 2025Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Most advanced cancers are treated with drug combinations. Rational design aims to identify synergistic combinations, but existing synergy metrics apply to preclinical, not clinical data. Here we propose a model of drug additivity for progression-free survival (PFS) to assess whether clinical efficacies of approved drug combinations are additive or synergistic. This model includes patient-to-patient variability in best single-drug response plus the weaker drug per patient. Among US Food and Drug Administration approvals of drug combinations for advanced cancers (1995-2020), 95% exhibited additive or less than additive effects on PFS times. Among positive or negative phase 3 trials published between 2014-2018, every combination that improved PFS was expected to succeed by additivity (100% sensitivity) and most failures were expected to fail (78% specificity). This study shows synergy is neither a necessary nor common property of clinically effective drug combinations. The predictable efficacy of approved combinations suggests that additivity can be a design principle for combination therapies.
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Registered trials
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.