Evidence map›Paper›PMID 39103633›Full record

ArticleNature chemical biology2025

Single-cell sensor analyses reveal signaling programs enabling Ras-G12C drug resistance.

Jason Z Zhang, Shao-En Ong, David Baker, Dustin J Maly

Abstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Review
  8. bioRxiv : the preprint server for biology · 2025
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

4 authors.

Jason Z ZhangDepartment of Biochemistry, University of Washington, Seattle, WA, USA. jason.zhang0428@gmail.com.ORCID 0000-0003-0091-6273
Shao-En OngDepartment of Pharmacology, University of Washington, Seattle, WA, USA.
David BakerDepartment of Biochemistry, University of Washington, Seattle, WA, USA.ORCID 0000-0001-7896-6217
Dustin J MalyDepartment of Biochemistry, University of Washington, Seattle, WA, USA.ORCID 0000-0003-0094-0177

Funding

New Molecular Probes For Protein KinasesR01GM086858 · NIGMS · UNIVERSITY OF WASHINGTON · PI MALY, DUSTIN J · 2008 to 2025
$5.5M
Supplement to DEFINING PATHWAY-SPECIFIC KINASE SIGNALING MODULES WITH PROTEOMICSR01GM129090 · NIGMS · UNIVERSITY OF WASHINGTON · PI ONG, SHAO-EN · 2019 to 2022
$1.7M
Chemical Genetic Analysis of RAS SignalingR01GM145011 · NIGMS · UNIVERSITY OF WASHINGTON · PI MALY, DUSTIN J · 2022 to 2025
$1.5M
A NanoLC-Orbitrap Tribrid Instrument for Comprehensive Proteomics AnalysesS10OD021502 · OD · UNIVERSITY OF WASHINGTON · PI ONG, SHAO-EN · 2017 to 2017
$906k
NIGMS NIH HHS R01 GM086858NIGMS NIH HHS R01 GM129090NIGMS NIH HHS R01 GM145011NIH HHS S10 OD021502U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01GM086858U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01GM145011U.S. Department of Health & Human Services | National Institutes of Health (NIH) S10OD021502
6 · The paper itself

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.

Indexed as

Biosensing TechniquesDrug Resistance, NeoplasmProto-Oncogene Proteins p21(ras)Signal TransductionSingle-Cell AnalysisAntineoplastic AgentsCell Line, TumorHumansMajor Vault ProteinMitochondriaVault Ribonucleoprotein ParticlesAntineoplastic AgentsKRAS protein, humanMajor Vault ProteinProto-Oncogene Proteins p21(ras)Vault Ribonucleoprotein Particles

Identifiers

PMID39103633
PMCPMC11666463

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Registered trials

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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.