ReviewCancer discovery2022
Independent Drug Action in Combination Therapy: Implications for Precision Oncology.
Review in Cancer discovery, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 161 papers, 2 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
161 citing papers in PubMed, 2 syntheses or guidelines pooled it, 284 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
- Impact of combinatorial immunotherapies in breast cancer: a systematic review and meta-analysis.Frontiers in immunology · 2024Pooled it
- 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
- Antitumor activity and structure-activity relationship of poly (ADP-ribose) polymerase (PARP)-based dual inhibitors.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- Transarterial chemoembolization (TACE) with or without immune checkpoint inhibitors in unresectable hepatocellular carcinoma: a meta-analysis of randomized clinical trials.ESMO gastrointestinal oncology · 2026Review
- Comparative Response of Canine and Human Osteosarcoma Tumour Cell Lines to Molecularly Targeted Anticancer Agents at Clinically Relevant Exposures With Analysis of Genomic Biomarkers.Veterinary and comparative oncology · 2026Article
- Chemotherapeutic Potential of Fluorouracil-Platinum (IV) Prodrugs Against Cisplatin-Resistant Colorectal Cancer Cells.Chemistry (Weinheim an der Bergstrasse, Germany) · 2026Article
- Bacteria-mimicking cancer cells reprogram macrophages via multiple pattern recognition receptor pathways for cancer immunotherapy.Signal transduction and targeted therapy · 2026Article
- Dual Inhibition of TRIP13 and Aurora A Induces Mitotic DNA Damage and Concurrent Pyroptotic-Apoptotic Cell Death in Rb-Deficient Cancer Cells.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- LIG1 Loss in TP53-mutant Triple Negative Breast Cancer Rewires DNA Repair and Confers Sensitivity to PARP-ATR Inhibitor Combinations.Molecular cancer therapeutics · 2026Article
- Pharmaceutical Compounding as a Pillar of Personalized Oncology: Current Applications, Emerging Technologies, and Future Perspectives.Pharmaceuticals (Basel, Switzerland) · 2026Review
- A disentangled transformer-based transfer learning framework to predict patient drug response from tumor single-cell transcriptomics.Bioinformatics (Oxford, England) · 2026Article
- 3D EM uncovers mitochondrial network remodeling in residual triple negative breast cancer after conventional chemotherapy treatments.iScience · 2026Article
- Metabolomic and Microbiome Profiling Reveals the Protective Mechanism ofInternational journal of molecular sciences · 2026Article
- Review
- Rethinking ovarian cancer III: the past decade and future directions.Nature reviews. Cancer · 2026Review
- Safety of fruquintinib mono- and combo therapy in metastatic colorectal cancer: real-world subgroup analysis from China.Future oncology (London, England) · 2026Article
- A causal inference framework for identifying essential genes to enhance drug synergy prediction.Bioinformatics (Oxford, England) · 2026Article
- Systematic interrogation of drug sensitivities in melanoma reveals potent synergistic and antagonistic drug combinations with translational potential.Communications medicine · 2026Article
101 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 3 institutions in 1 country.
Funding
Abstract
Combination therapies are superior to monotherapy for many cancers. This advantage was historically ascribed to the ability of combinations to address tumor heterogeneity, but synergistic interaction is now a common explanation as well as a design criterion for new combinations. We review evidence that independent drug action, described in 1961, explains the efficacy of many practice-changing combination therapies: it provides populations of patients with heterogeneous drug sensitivities multiple chances of benefit from at least one drug. Understanding response heterogeneity could reveal predictive or pharmacodynamic biomarkers for more precise use of existing drugs and realize the benefits of additivity or synergy. SIGNIFICANCE: The model of independent drug action represents an effective means to predict the magnitude of benefit likely to be observed in new clinical trials for combination therapies. The "bet-hedging" strategy implicit in independent action suggests that individual patients often benefit from only a subset-sometimes one-of the drugs in a combination. Personalized, targeted combination therapy, consisting of agents likely to be active in a particular patient, will increase, perhaps substantially, the magnitude of therapeutic benefit. Precision approaches of this type will require a better understanding of variability in drug response and new biomarkers, which will entail preclinical research on diverse panels of cancer models rather than studying drug synergy in unusually sensitive models.
Indexed as
Identifiers
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.