ArticleNPJ precision oncology2022
The landscape of therapeutic vulnerabilities in EGFR inhibitor osimertinib drug tolerant persister cells.
Article in NPJ precision oncology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
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The trial behind it
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Who cites it
36 citing papers in PubMed, 38 citations in OpenAlex.
- Persistent TOP1 cleavage complexes in drug-tolerant cells drive adaptive resistance to EGFR-targeted therapies in lung cancer.Science advances · 2026Article
- Transcriptomic and network analyses identify epigenetic regulators of drug-tolerant persister (DTP) subsets in EGFR-mutant HCC827 non-small cell lung cancer.Genes & genomics · 2026Article
- Tumor Plasticity and Microenvironmental Crosstalk as Drivers of Metastasis and Therapy Resistance.MedComm · 2026Review
- ResMap: A community resource for systematic mapping of therapy-persistent residual cancer cell dependencies across contexts.Science advances · 2026Article
- H4K8 lactylation-mediated ferroptosis defense drives EGFR-TKI resistance in lung adenocarcinoma.Apoptosis : an international journal on programmed cell death · 2026Article
- Bidirectional coupling among EMT, AXL-RB1 signaling and lineage switch drives resistance to osimertinib and worse clinical outcomes in NSCLC.bioRxiv : the preprint server for biology · 2026Article
- Propionate metabolism is dysregulated in non-small cell lung cancer patients and EGFR-mutant drug-tolerant persister cells.Scientific reports · 2026Article
- MicroRNA Mimics Based on the miR-15/107 Consensus Sequence Sensitise NSCLC Cells to Targeted Therapy.International journal of molecular sciences · 2026Article
- Mitochondrial niches of residual disease in EGFR-mutant NSCLC: immune-constrained persistence and therapeutic interception.Frontiers in immunology · 2026Review
- Drug-tolerant persister cells in cancer: a scoping review of definitions, models, and molecular mechanisms.Frontiers in oncology · 2026Review
- Drug-tolerant persister cells in lymphoid malignancies: from mechanisms to therapeutic opportunities.Frontiers in oncology · 2026Review
- Targeting tumor transition windows.Exploration of targeted anti-tumor therapy · 2026Review
- MUCIN 1 confers inflammatory memory of tyrosine kinase inhibitor resistance in non-small cell lung cancer.Signal transduction and targeted therapy · 2025Article
- SOS1 inhibition suppresses the emergence of osimertinib resistance to generate a durable response inScience signaling · 2025Article
- TKI resistance related genes in LUAD predict patient prognosis and tumor immune microenvironment with LHX2 as a hub gene.Discover oncology · 2025Article
- ZDHHC11-mediated AXL palmitoylation promotes osimertinib resistance in non-small-cell lung cancer.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Phosphoproteomics of osimertinib-tolerant persister cells reveals targetable kinase-substrate signatures.Molecular systems biology · 2025Article
- Propionate metabolism dysregulation promotes drug-tolerant persister cell survival in non-small cell lung cancer.bioRxiv : the preprint server for biology · 2025Article
- Restoration of Osimertinib sensitivity in lung cancer through BRD4 inhibitor-mediated depalmitoylation of mutant EGFR via APT1.NPJ precision oncology · 2025Article
- Article
Corrections and comments
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Authors and funding
20 authors at 4 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Third-generation EGFR tyrosine kinase inhibitors (EGFR-TKIs), including osimertinib, an irreversible EGFR-TKI, are important treatments for non-small cell lung cancer with EGFR-TKI sensitizing or EGFR T790M resistance mutations. While patients treated with osimertinib show clinical benefit, disease progression and drug resistance are common. Emergence of de novo acquired resistance from a drug tolerant persister (DTP) cell population is one mechanism proposed to explain progression on osimertinib and other targeted cancer therapies. Here we profiled osimertinib DTPs using RNA-seq and ATAC-seq to characterize the features of these cells and performed drug screens to identify therapeutic vulnerabilities. We identified several vulnerabilities in osimertinib DTPs that were common across models, including sensitivity to MEK, AURKB, BRD4, and TEAD inhibition. We linked several of these vulnerabilities to gene regulatory changes, for example, TEAD vulnerability was consistent with evidence of Hippo pathway turning off in osimertinib DTPs. Last, we used genetic approaches using siRNA knockdown or CRISPR knockout to validate AURKB, BRD4, and TEAD as the direct targets responsible for the vulnerabilities observed in the drug screen.
Identifiers
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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.