ArticleNature chemical biology2025
Single-cell sensor analyses reveal signaling programs enabling Ras-G12C drug resistance.
Article in Nature chemical biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- A chemigenetic endogenous Ras activity biosensor for live-cell pharmacology.Nature chemical biology · 2026Article
- Modular Input-Output Biosensor Design UsingACS sensors · 2026Article
- Review
- De novo design of Ras isoform selective binders.Cell chemical biology · 2026Article
- A Modular Platform for the Optogenetic Control of Small GTPase Activity in Living Cells Reveals Long-Range RhoA Signaling.bioRxiv : the preprint server for biology · 2025Article
- Wild-type RAS signaling is an essential therapeutic target inScience signaling · 2025Article
- The Role of AI-Driven De Novo Protein Design in the Exploration of the Protein Functional Universe.Biology · 2025Review
- Article
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Abstract
Clinical resistance to rat sarcoma virus (Ras)-G12C inhibitors is a challenge. A subpopulation of cancer cells has been shown to undergo genomic and transcriptional alterations to facilitate drug resistance but the immediate adaptive effects on Ras signaling in response to these drugs at the single-cell level is not well understood. Here, we used Ras biosensors to profile the activity and signaling environment of endogenous Ras at the single-cell level. We found that a subpopulation of KRas-G12C cells treated with Ras-G12C-guanosine-diphosphate inhibitors underwent adaptive signaling and metabolic changes driven by wild-type Ras at the Golgi and mutant KRas at the mitochondria, respectively. Our Ras biosensors identified major vault protein as a mediator of Ras activation through its scaffolding of Ras signaling pathway components and metabolite channels. Overall, methods including ours that facilitate direct analysis on the single-cell level can report the adaptations that subpopulations of cells adopt in response to cancer therapies, thus providing insight into drug resistance.
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