Evidence map›Paper›PMID 41735640›Full record

ArticleNature cancer2026

The GENEVA platform models tumor mosaicism to reveal variations of responses to KRAS inhibitors and identify improved drug combinations.

Johnny X Yu, Jung Min Suh, Katerina D Popova, Kristle Garcia, Tanvi Joshi, Bruce Culbertson, Jessica B Spinelli, Vishvak Subramanyam, Kevin Lou, Trey Charbonneau and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors.

Johnny X Yu *Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA.
Jung Min Suh *Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-1210-8460
Katerina D PopovaBiomedical Sciences Graduate Program, University of California, San Francsicso, San Francisco, CA, USA.
Kristle GarciaDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-9868-8397
Tanvi JoshiDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0009-0001-5051-7927
Bruce CulbertsonDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA.
Jessica B SpinelliProgram in Molecular Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.ORCID http://orcid.org/0000-0003-3657-4578
Vishvak SubramanyamDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA.
Kevin LouBiomedical Sciences Graduate Program, University of California, San Francsicso, San Francisco, CA, USA.ORCID http://orcid.org/0000-0003-4939-4381
Trey CharbonneauArc Institute, Palo Alto, CA, USA.
Kevan M ShokatBiomedical Sciences Graduate Program, University of California, San Francsicso, San Francisco, CA, USA.ORCID http://orcid.org/0000-0001-8590-7741
Jonathan WeissmanDepartment of Biology, Whitehead Institute, MIT, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-2445-670X
Hani GoodarziDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA. hani.goodarzi@ucsf.edu.ORCID http://orcid.org/0000-0002-9648-8949

Funding

Restorative practice in repairing harm and promoting safe and inclusive practices in the laboratory.T32GM136547 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Adrian Erlebacher, Anita Sil · 2020 to 2026
$4.5M
Investigating functional interactions with KRAS G12C inhibitionF30CA239476 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LOU, KEVIN · 2019 to 2021
$131k
National Science Foundation (NSF) GRFPNIGMS NIH HHS T32 GM136547UC | UC San Francisco | School of Medicine, University of California, San Francisco (UCSF School of Medicine) Program for Breakthrough Biomedical ResearchUC | UC San Francisco | School of Medicine, University of California, San Francisco (UCSF School of Medicine) RRP IMIAU.S. Department of Health & Human Services | National Institutes of Health (NIH) 1S10OD028511-01U.S. Department of Health & Human Services | National Institutes of Health (NIH) 5R01CA244550U.S. Department of Health & Human Services | National Institutes of Health (NIH) F30CA239476
6 · The paper itself

Abstract

The clinical success of cancer drug candidates depends on efficacy across many different individuals. Because xenografts are challenging to scale, we currently rely on a limited set of in vivo preclinical models. Here, to address this limitation, we introduce GENEVA, a scalable single-cell-resolution platform for measuring responses to drug perturbations. GENEVA models cancer genetic diversity by combining multiple patient-derived cell lines and cancer cell lines into pooled three-dimensional cultures and xenograft models, allowing us to study drug responses across a wide range of genetic backgrounds within a single experiment. We apply GENEVA to investigate KRAS-G12C inhibitors and demonstrate that mitochondrial activation is a key driver of cell death following KRAS inhibition, while epithelial-to-mesenchymal transition is a prominent resistance mechanism. These findings highlight the utility of GENEVA to identify therapeutic targets and optimize combination therapies with the potential to bridge the gap between preclinical cancer models and patient outcomes.

Indexed as

Antineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsMosaicismNeoplasmsProto-Oncogene Proteins p21(ras)AnimalsCell Line, TumorDrug Resistance, NeoplasmEpithelial-Mesenchymal TransitionFemaleHumansMiceXenograft Model Antitumor AssaysAntineoplastic AgentsKRAS protein, humanProto-Oncogene Proteins p21(ras)

Identifiers

PMID41735640
PMCPMC13035475

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.