ArticleCell2017
Combination Cancer Therapy Can Confer Benefit via Patient-to-Patient Variability without Drug Additivity or Synergy.
Article in Cell, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 391 papers, 4 of them syntheses that pooled 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.
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.
Who cites it
391 citing papers in PubMed, 4 syntheses or guidelines pooled it, 647 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
- Exercise and pathologic complete response to cancer treatment: a systematic review and meta-analysis.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2026Pooled it
- Rice bran arabinoxylan compound as a natural product for cancer treatment - an evidence-based assessment of the effects and mechanisms.Pharmaceutical biology · 2024Pooled it
- Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of melanoma, version 3.0.Journal for immunotherapy of cancer · 2023Guideline
- Coupling of response biomarkers between tumor and peripheral blood in patients undergoing chemoimmunotherapy.Cell reports. Medicine · 2025Trial
- Phase II Study of Eribulin plus Pembrolizumab in Metastatic Soft-tissue Sarcomas: Clinical Outcomes and Biological Correlates.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Trial
- The phosphatidylserine targeting antibody bavituximab plus pembrolizumab in unresectable hepatocellular carcinoma: a phase 2 trial.Nature communications · 2024Trial
- A systematic assessment of the short- and long-term effects of commonly used breast cancer chemotherapeutics on the gut microbiome‒blood‒brain axis of female mice.Gut microbes · 2026Article
- Host chromatin architecture in HPV-driven cervical cancer: molecular mechanisms and therapeutic resistance.Medical oncology (Northwood, London, England) · 2026Review
- Octreotide-Mediated Co-Solubilization of Paclitaxel and Docetaxel: A Novel Targeted Formulation for Synergistic Anticancer Chemotherapy.Pharmaceutics · 2026Article
- Bladder cancer precision-cut tumor slices (PCTS) preserve functional immune microenvironment enabling ex vivo drug evaluation.BMC medicine · 2026Article
- 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
- Functional profiling of ovarian cancer models reveals Bcl-xL/NOTCH targeting to overcome resistance.NPJ precision oncology · 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
- Systematic design of combination therapy by targeting master regulators of coexisting diffuse midline glioma cell states.Nature genetics · 2026Article
- Innovative immunotherapy approaches: harnessing synergy of dual checkpoint blockade in oncology.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- A shape-constrained regression and wild bootstrap framework for reproducible drug synergy testing.bioRxiv : the preprint server for biology · 2026Article
- Innovative In Vitro-In Silico Platform for Dose-Response Modeling in Canine Bladder Cancer: A 3D Organoid- and Mathematics-Based Approach.The AAPS journal · 2026Article
- TYK2 mediates neuroinflammation in Alzheimer's disease brains with TDP-43 pathology.Nature communications · 2026Article
331 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Combination cancer therapies aim to improve the probability and magnitude of therapeutic responses and reduce the likelihood of acquired resistance in an individual patient. However, drugs are tested in clinical trials on genetically diverse patient populations. We show here that patient-to-patient variability and independent drug action are sufficient to explain the superiority of many FDA-approved drug combinations in the absence of drug synergy or additivity. This is also true for combinations tested in patient-derived tumor xenografts. In a combination exhibiting independent drug action, each patient benefits solely from the drug to which his or her tumor is most sensitive, with no added benefit from other drugs. Even when drug combinations exhibit additivity or synergy in pre-clinical models, patient-to-patient variability and low cross-resistance make independent action the dominant mechanism in clinical populations. This insight represents a different way to interpret trial data and a different way to design combination therapies.
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What OpenQuestion holds
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.