ArticleNature chemical biology2020
Drug antagonism and single-agent dominance result from differences in death kinetics.
Article in Nature chemical biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 43 citations in OpenAlex.
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- Comprehensive Analysis of Drug Response using the FLICK Assay.Journal of visualized experiments : JoVE · 2025Article
- MEDUSA for Identifying Death Regulatory Genes in Chemo-genetic Profiling Data.Journal of visualized experiments : JoVE · 2025Article
- Evaluating Blood-Brain Barrier Permeability, Cytotoxicity, and Activity of Potential Acetylcholinesterase Inhibitors: In Vitro and In Silico Study.Pharmacology research & perspectives · 2024Article
- Biological Nitrification Inhibitors with Antagonistic and Synergistic Effects on Growth of Ammonia Oxidisers and Soil Nitrification.Microbial ecology · 2024Article
- Functional genomic screens with death rate analyses reveal mechanisms of drug action.Nature chemical biology · 2024Article
- The death gaze of MEDUSA.Nature chemical biology · 2024Article
- Functional genomics reveals an off-target dependency of drug synergy in gastric cancer therapy.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2024Article
- Alkaloid-Based Isoxazolylureas: Synthesis and Effect in Combination with Anticancer Drugs on C6 Rat Glioma Model Cells.Molecules (Basel, Switzerland) · 2024Article
- Ultrasensitive Response Explains the Benefit of Combination Chemotherapy Despite Drug Antagonism.Molecular cancer therapeutics · 2024Article
- Inhibitory effect of temozolomide on apoptosis induction of cinnamaldehyde in human glioblastoma multiforme T98G cell line.Anatomy & cell biology · 2024Article
- Critical role of growth medium for detecting drug interactions in Gram-negative bacteria that modelmBio · 2024Article
- Quick tips for interpreting cell death experiments.Nature cell biology · 2023Article
- Functional genomics reveals an off-target dependency of drug synergy in gastric cancer therapy.bioRxiv : the preprint server for biology · 2023Article
- Mapping resistance-associated anthelmintic interactions in the model nematode Caenorhabditis elegans.PLoS neglected tropical diseases · 2023Article
- Effect of storage age and containers on the physicochemical degradation of guggul oleo-resin.Scientific reports · 2023Article
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Authors and funding
8 authors at 1 institution in 1 country.
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Abstract
Cancer treatment generally involves drugs used in combinations. Most previous work has focused on identifying and understanding synergistic drug-drug interactions; however, understanding antagonistic interactions remains an important and understudied issue. To enrich for antagonism and reveal common features of these combinations, we screened all pairwise combinations of drugs characterized as activators of regulated cell death. This network is strongly enriched for antagonism, particularly a form of antagonism that we call 'single-agent dominance'. Single-agent dominance refers to antagonisms in which a two-drug combination phenocopies one of the two agents. Dominance results from differences in cell death onset time, with dominant drugs acting earlier than their suppressed counterparts. We explored mechanisms by which parthanatotic agents dominate apoptotic agents, finding that dominance in this scenario is caused by mutually exclusive and conflicting use of Poly(ADP-ribose) polymerase 1 (PARP1). Taken together, our study reveals death kinetics as a predictive feature of antagonism, due to inhibitory crosstalk between cell death pathways.
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