ArticleScience advances2024
Conditional lethality profiling reveals anticancer mechanisms of action and drug-nutrient interactions.
Article in Science advances, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- The microenvironment dictates glyco-immune surveillance via HSF1-mediated metabolism.Science advances · 2026Article
- Protocol to isolate and co-culture primary mouse hepatocytes, hepatic stellate cells, and Kupffer cells under physiological conditions.STAR protocols · 2026Article
- Proteomic Profiling Reveals How Physiological Media Reshape Cancer Cell Proteomes and Signaling Networks.Molecular & cellular proteomics : MCP · 2026Article
- Metformin suppressed epithelial-mesenchymal transition, cisplatin resistance and metastatic potential of ovarian cancer via inhibiting TGF-β1/Smads.Translational cancer research · 2026Article
- A multi-omic approach reveals iron availability influences cell fate fidelity.npj metabolic health and disease · 2026Article
- Tumor nutrient stress gives rise to a drug tolerant cell state in pancreatic cancer.bioRxiv : the preprint server for biology · 2025Article
- Classically activated macrophages undergo functionally significant nucleotide metabolism remodelling driven by nitric oxide.Nature metabolism · 2025Article
- Metabolic Imprint of Poliovirus on Glioblastoma Cells and Its Role in Virus Replication and Cytopathic Activity.International journal of molecular sciences · 2025Article
- Cytosolic NADK is conditionally essential for folate-dependent nucleotide synthesis.Nature metabolism · 2025Article
- MultiplexedbioRxiv : the preprint server for biology · 2025Article
- Refined culture conditions with increased physiological relevance uncover oncogene-dependent metabolic signatures in Ewing sarcoma spheroids.Cell reports methods · 2025Article
- De Novo Purine Metabolism is a Metabolic Vulnerability of Cancers with Low p16 Expression.Cancer research communications · 2024Article
- The microenvironment dictates glycocalyx construction and immune surveillance.Research square · 2023Article
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Abstract
Chemical screens across hundreds of cell lines have shown that the drug sensitivities of human cancers can vary by genotype or lineage. However, most drug discovery studies have relied on culture media that poorly reflect metabolite levels in human blood. Here, we perform drug screens in traditional and Human Plasma-Like Medium (HPLM). Sets of compounds that show conditional anticancer activity span different phases of global development and include non-oncology drugs. Comparisons of the synthetic and serum-derived components that comprise typical media trace sets of conditional phenotypes to nucleotide synthesis substrates. We also characterize a unique dual mechanism for brivudine, a compound approved for antiviral use. Brivudine selectively impairs cell growth in low folate conditions by targeting two enzymes involved in one-carbon metabolism. Cataloged gene essentiality data further suggest that conditional phenotypes for other compounds are linked to off-target effects. Our findings establish general strategies for identifying drug-nutrient interactions and mechanisms of action by exploiting conditional lethality in cancer cells.
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