ArticleeLife2019
A curative combination cancer therapy achieves high fractional cell killing through low cross-resistance and drug additivity.
Article in eLife, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers.
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.
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Who cites it
86 citing papers in PubMed, 139 citations in OpenAlex.
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- Functional genomics and proteomics identify Folate Carrier SLC19A1 as a predictor of pralatrexate sensitivity in diverse T-cell lymphoma models.Molecular cancer therapeutics · 2026Article
- Rethinking the role of synergy calculations in the next century of drug combination discovery.Med (New York, N.Y.) · 2026Review
- Experimentally calibrated multiscale model predicts schedule dependent drug combination effects.NPJ systems biology and applications · 2026Article
- DeepDrugs: a mechanism-aware tri-linear attention framework for synergistic drug-combination prediction.Briefings in bioinformatics · 2026Article
- Volumetric mechanoplasticity couples melanoma drug tolerance to susceptibility to CD8bioRxiv : the preprint server for biology · 2026Article
- Ribosome-associated quality control of aberrant protein production during amino acid limitation.bioRxiv : the preprint server for biology · 2026Article
- Past present and future of radiosensitization in cervical cancer.Frontiers in oncology · 2026Review
- Mechanisms of first-line treatment resistance in diffuse large B-cell lymphoma.Frontiers in immunology · 2026Review
- Proteomic Study of Diffuse Large B-Cell Lymphoma Identifying Proteins Associated with R-CHOP Response.Biomedicines · 2025Article
- Repurposing Asparaginase Therapy to Target Cisplatin-Resistant Cancer Cells.Fundamental & clinical pharmacology · 2025Article
- Article
- Systematic profiling of cancer-fibroblast interactions reveals drug combinations in ovarian cancer.Molecular oncology · 2025Article
- Computational modelling of aggressive B-cell lymphoma.Biochemical Society transactions · 2025Review
- A Model of Intratumor and Interpatient Heterogeneity Explains Clinical Trials of Curative Combination Therapy for Lymphoma.Blood cancer discovery · 2025Article
- Programming tumor evolution with selection gene drives to proactively combat drug resistance.Nature biotechnology · 2025Article
- Chlorogenic Acid Enhances Beta-Lapachone-Induced Cell Death by Suppressing Autophagy in NQO1-Positive Cancer Cells.Cell biology international · 2025Article
- Potential Benefits of Adding Alendronate, Celecoxib, Itraconazole, Ramelteon, and Simvastatin to Endometrial Cancer Treatment: The EC5 Regimen.Current issues in molecular biology · 2025Article
- A Bayesian active learning platform for scalable combination drug screens.Nature communications · 2025Article
26 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 1 institution in 1 country.
Funding
Abstract
Curative cancer therapies are uncommon and nearly always involve multi-drug combinations developed by experimentation in humans; unfortunately, the mechanistic basis for the success of such combinations has rarely been investigated in detail, obscuring lessons learned. Here, we use isobologram analysis to score pharmacological interaction, and clone tracing and CRISPR screening to measure cross-resistance among the five drugs comprising R-CHOP, a combination therapy that frequently cures Diffuse Large B-Cell Lymphomas. We find that drugs in R-CHOP exhibit very low cross-resistance but not synergistic interaction: together they achieve a greater fractional kill according to the null hypothesis for both the Loewe dose-additivity model and the Bliss effect-independence model. These data provide direct evidence for the 50 year old hypothesis that a curative cancer therapy can be constructed on the basis of independently effective drugs having non-overlapping mechanisms of resistance, without synergistic interaction, which has immediate significance for the design of new drug combinations.
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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.