ArticleCancer science2023
Notch pathway regulates osimertinib drug-tolerant persistence in EGFR-mutated non-small-cell lung cancer.
Article in Cancer science, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- Pooled it
- 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
- Lineage plasticity: a new dilemma in lung cancer treatment.Molecular biology reports · 2026Review
- Furmonertinib plus pemetrexed in the treatment ofFrontiers in oncology · 2026Article
- Mitochondrial niches of residual disease in EGFR-mutant NSCLC: immune-constrained persistence and therapeutic interception.Frontiers in immunology · 2026Review
- SOS1 inhibition suppresses the emergence of osimertinib resistance to generate a durable response inScience signaling · 2025Article
- N6-methyladenosine-modified GPX2 impacts cancer cell stemness and TKI resistance through regulating of redox metabolism.Cell death & disease · 2025Article
- Drug-induced tolerant persisters in tumor: mechanism, vulnerability and perspective implication for clinical treatment.Molecular cancer · 2025Review
- DUSP1 Promotes Osimertinib Drug-Tolerant Persistence by Inhibiting MAPK/ERK Signaling in Non-small Cell Lung Cancer.Molecular biotechnology · 2025Article
- Canonical and noncanonical NOTCH signaling in the nongenetic resistance of cancer: distinct and concerted control.Frontiers of medicine · 2025Review
- Hes1 in malignant tumors: from molecular mechanism to therapeutic potential.Frontiers in immunology · 2025Review
- Pralatrexate represses the resistance of HCC cells to molecular targeted agents via the miRNA-34a/Notch pathway.Discover oncology · 2024Article
- Examining the contribution of Notch signaling to lung disease development.Naunyn-Schmiedeberg's archives of pharmacology · 2024Review
- Research into overcoming drug resistance in lung cancer treatment using CRISPR-Cas9 technology: a narrative review.Translational lung cancer research · 2024Review
- Drug tolerant persister cell plasticity in cancer: A revolutionary strategy for more effective anticancer therapies.Signal transduction and targeted therapy · 2024Review
- Therapeutic advances of targeting receptor tyrosine kinases in cancer.Signal transduction and targeted therapy · 2024Review
- Targeting of drug-tolerant persister cells as an approach to counter drug resistance in non-small cell lung cancer.Lung cancer (Amsterdam, Netherlands) · 2024Review
- NOTCH1 and CREBBP co-mutations negatively affect the benefit of adjuvant therapy in completely resected EGFR-mutated NSCLC: translational research of phase III IMPACT study.Molecular oncology · 2024Article
- Diapause-like Drug-Tolerant Persister State: The Key to Nirvana Rebirth.Medicina (Kaunas, Lithuania) · 2024Review
- Microvascular rarefaction caused by the NOTCH signaling pathway is a key cause of TKI-apatinib-induced hypertension and cardiac damage.Frontiers in pharmacology · 2024Review
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Osimertinib is a third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) that has shown marked antitumor activity in patients with EGFR-mutated non-small-cell lung cancer (NSCLC). However, these effects are transient and most patients develop resistance. Reversible drug-tolerant persister (DTP) cells are defined as a small subpopulation of cells with markedly reduced sensitivity and non-genetic acquired resistance to EGFR-TKIs. Notch is a transmembrane receptor that plays an important role in tumorigenesis. We previously reported that there is significant crosstalk between the Notch and EGFR pathways in NSCLC. Moreover, the Notch pathway is associated with resistance to previous-generation EGFR-TKIs. However, the role of Notch in osimertinib resistance is not fully understood. In this study, we evaluated whether Notch is involved in osimertinib resistance. We show that NOTCH1 and Notch target genes are upregulated in osimertinib DTP cells, and that the addition of a γ-secretase inhibitor (GSI), a Notch inhibitor, impairs drug-tolerant persistence in vitro and in vivo. Compared with osimertinib, combined GSI and osimertinib suppress phospho-ERK partly by enhancing DUSP1 expression. Furthermore, Notch1 and HES1 were upregulated after EGFR-TKI treatment in half of human EGFR-mutated NSCLC tumor tissues. These results suggest that the combination of GSI and osimertinib may be a potential therapy for EGFR-mutated NSCLC.
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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 Socratic graph.