ArticleNature communications2023
Oncogenic context shapes the fitness landscape of tumor suppression.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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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.
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.
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Who cites it
25 citing papers in PubMed, 30 citations in OpenAlex.
- Lineage identity governs oncogene dependence in mouse NSCLC models of KRAS inhibitor resistance.Nature genetics · 2026Article
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- Engineered bacteria as exogenous organelle mimics restore PTEN and p53 tumor suppressor functions for cancer therapy.Nature communications · 2026Article
- Tumor suppressor genotype influences the extent and mode of immunosurveillance in lung cancer.Nature communications · 2026Article
- Mutant KRAS vaccine with dual checkpoint blockade in resected pancreatic cancer: a phase I trial.Nature communications · 2026Article
- PSMC4 promotes low-grade glioma progression and predicts poor prognosis.European journal of medical research · 2026Article
- EML4-ALK Variant-Specific Genetic Interactions Shape Lung Tumorigenesis.Cancer discovery · 2026Article
- Integrated in vivo combinatorial functional genomics and spatial transcriptomics of tumours to decode genotype-to-phenotype relationships.Nature biomedical engineering · 2026Article
- Integrative multiomic approaches reveal ZMAT3 and p21 as conserved hubs in the p53 tumor suppression network.Cell death and differentiation · 2025Article
- Mutations in tumor signaling, metastases, and synthetic lethality establish distinct patterns.PLoS computational biology · 2025Article
- Evaluating variant pathogenicity prediction tools to establish African inclusive guidelines for germline genetic testing.Communications medicine · 2025Article
- Translating premalignant biology to accelerate non-small-cell lung cancer interception.Nature reviews. Cancer · 2025Review
- A STAG2-PAXIP1/PAGR1 axis suppresses lung tumorigenesis.The Journal of experimental medicine · 2025Article
- Context-dependent effects of CDKN2A and other 9p21 gene losses during the evolution of esophageal cancer.Nature cancer · 2025Article
- MicroRNAs and lung cancer: overview of essential pathways and somatic mutations in cancer progression.Frontiers in oncology · 2025Review
- Translational and Therapeutic Evaluation of RAS-GTP Inhibition by RMC-6236 in RAS-Driven Cancers.Cancer discovery · 2024Article
- Review
- Response to: Comment on Genetic Ancestry-Specific Molecular and Survival Differences in Admixed Breast Cancer Patients.Annals of surgery open : perspectives of surgical history, education, and clinical approaches · 2024Article
- Co-occurring Mutations in Different Genes Can Fuel Oncogenic Signaling and Serve as Metastatic Tumor Markers.bioRxiv : the preprint server for biology · 2024Article
- How CRISPR Is Revolutionizing the Generation of New Models for Cancer Research.Cold Spring Harbor perspectives in medicine · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
24 authors at 9 institutions in 2 countries.
Funding
Abstract
Tumors acquire alterations in oncogenes and tumor suppressor genes in an adaptive walk through the fitness landscape of tumorigenesis. However, the interactions between oncogenes and tumor suppressor genes that shape this landscape remain poorly resolved and cannot be revealed by human cancer genomics alone. Here, we use a multiplexed, autochthonous mouse platform to model and quantify the initiation and growth of more than one hundred genotypes of lung tumors across four oncogenic contexts: KRAS G12D, KRAS G12C, BRAF V600E, and EGFR L858R. We show that the fitness landscape is rugged-the effect of tumor suppressor inactivation often switches between beneficial and deleterious depending on the oncogenic context-and shows no evidence of diminishing-returns epistasis within variants of the same oncogene. These findings argue against a simple linear signaling relationship amongst these three oncogenes and imply a critical role for off-axis signaling in determining the fitness effects of inactivating tumor suppressors.
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Registered trials
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.