ArticleeLife2015
Evidence that synthetic lethality underlies the mutual exclusivity of oncogenic KRAS and EGFR mutations in lung adenocarcinoma.
Article in eLife, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 121 papers, 1 of them a synthesis that pooled it.
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
121 citing papers in PubMed, 1 synthesis or guideline pooled it, 199 citations in OpenAlex.
- Multi-modal meta-analysis of cancer cell line omics profiles identifies ECHDC1 as a novel breast tumor suppressor.Molecular systems biology · 2021Pooled it
- Variant-Specific Landscape of Mutual Exclusivity Among BRAF, EGFR, and KRAS Oncogenes Reveals Overlap With Functionally Antagonistic Mutant Pairs.International journal of cancer · 2026Article
- Empowering Inference of Epistasis on the Basis of Mutual Exclusivity, Co-Occurrence, Functional Antagonism and Synergy in ERK-Pathway Oncogenes.International journal of cancer · 2026Article
- The Role of KRAS in Non-Small Cell Lung Cancer: From Molecular Background to Precision Medicine.International journal of molecular sciences · 2026Review
- Context-dependent synthetic lethality - an emerging precision therapeutic approach.Nature reviews. Cancer · 2026Review
- Article
- ERKed by too much signaling: from oncogenic driver to therapeutic vulnerability.Cellular and molecular life sciences : CMLS · 2026Review
- Pan-cancer multi-omic ERBB2-HER2 characterization using next-generation sequencing and quantitative proteomics.NPJ precision oncology · 2026Article
- A Scalable Design for Proximity-Inducing Molecules.bioRxiv : the preprint server for biology · 2026Article
- Concurrent PIK3CA mutant promotes cachexia through inflammatory signaling in EGFR mutant lung cancer.Nature communications · 2025Article
- The pathogenic mutations in smokers with non-small cell lung cancer: a next-generation sequencing study.Translational lung cancer research · 2025Article
- Dual-Specificity Protein Phosphatases Targeting Extracellular Signal-Regulated Kinases: Friends or Foes in the Biology of Cancer?International journal of molecular sciences · 2025Review
- Drug tolerance and persistence to EGFR inhibitor treatment are mediated by an ILK-SFK-YAP signaling axis in lung adenocarcinoma.Oncogene · 2025Article
- Erk1Oncogene · 2025Article
- Metastatic small cell lung cancer arises from TP53/RB1-deficient and MYC overproduction hESC-derived PNECs.eLife · 2025Article
- Review
- Article
- Lethal co-expression intolerance underlies the mutually exclusive expression of ASCL1 and NEUROD1 in SCLC cells.NPJ precision oncology · 2025Article
- Potential promising of synthetic lethality in cancer research and treatment.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Comprehensive structure-function analysis reveals gain- and loss-of-function mechanisms impacting oncogenic KRAS activity.bioRxiv : the preprint server for biology · 2024Article
61 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Human lung adenocarcinomas (LUAD) contain mutations in EGFR in ∼15% of cases and in KRAS in ∼30%, yet no individual adenocarcinoma appears to carry activating mutations in both genes, a finding we have confirmed by re-analysis of data from over 600 LUAD. Here we provide evidence that co-occurrence of mutations in these two genes is deleterious. In transgenic mice programmed to express both mutant oncogenes in the lung epithelium, the resulting tumors express only one oncogene. We also show that forced expression of a second oncogene in human cancer cell lines with an endogenous mutated oncogene is deleterious. The most prominent features accompanying loss of cell viability were vacuolization, other changes in cell morphology, and increased macropinocytosis. Activation of ERK, p38 and JNK in the dying cells suggests that an overly active MAPK signaling pathway may mediate the phenotype. Together, our findings indicate that mutual exclusivity of oncogenic mutations may reveal unexpected vulnerabilities and therapeutic possibilities.
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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.