ArticleThe Journal of clinical investigation2020
Notch inhibition overcomes resistance to tyrosine kinase inhibitors in EGFR-driven lung adenocarcinoma.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed.
- NOTCH1 intracellular domain stabilization by MDM2 plays a major role in NSCLC response to platinum.EMBO molecular medicine · 2026Article
- A 10-pathway burden score complements tumor mutational burden for outcome stratification in non-small cell lung cancer.Frontiers in medicine · 2026Article
- The Predictive Value ofCurrent medical imaging · 2026Article
- TAF1 acetyltransferase promotes colorectal carcinoma metastasis by catalyzing β-hydroxybutyrylation of KCTD9.Oncogene · 2026Article
- Non-canonical NOTCH1 signaling regulates ferroptosis vulnerability in dormant lung cancer cells with stable resistance.Cell death & disease · 2025Article
- Significance of Notch Signaling in Salivary Gland Development and Diseases.Journal of clinical medicine · 2025Review
- 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
- TRIM59/RBPJ positive feedback circuit confers gemcitabine resistance in pancreatic cancer by activating the Notch signaling pathway.Cell death & disease · 2024Article
- Perivascular NOTCH3+ Stem Cells Drive Meningioma Tumorigenesis and Resistance to Radiotherapy.Cancer discovery · 2024Article
- Partial role of volatile organic compounds in behavioural responses of mice to bedding from cancer-affected congeners.Biology open · 2024Article
- Evolutionary proteogenomic landscape from pre-invasive to invasive lung adenocarcinoma.Cell reports. Medicine · 2024Article
- Transcriptomic analysis ofFrontiers in oncology · 2024Article
- Urinary VOCs as biomarkers of early stage lung tumour development in mice.Cancer biomarkers : section A of Disease markers · 2024Article
- Osimertinib as first-line treatment for recurrent lung cancer patients withJournal of thoracic disease · 2023Article
- Resistance of Lung Cancer to EGFR-Specific Kinase Inhibitors: Activation of Bypass Pathways and Endogenous Mutators.Cancers · 2023Review
- DLBCL-associated NOTCH2 mutations escape ubiquitin-dependent degradation and promote chemoresistance.Blood · 2023Article
- Early stage gastric adenocarcinoma: clinical and molecular landscapes.Nature reviews. Clinical oncology · 2023Review
- Notch pathway regulates osimertinib drug-tolerant persistence in EGFR-mutated non-small-cell lung cancer.Cancer science · 2023Article
- Volumetric parameters of the primary tumor and whole-body tumor burden derived from baselineEuropean journal of hybrid imaging · 2022Article
Corrections and comments
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Authors and funding
26 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
EGFR-mutated lung adenocarcinoma patients treated with gefitinib and osimertinib show a therapeutic benefit limited by the appearance of secondary mutations, such as EGFRT790M and EGFRC797S. It is generally assumed that these secondary mutations render EGFR completely unresponsive to the inhibitors, but contrary to this, we uncovered here that gefitinib and osimertinib increased STAT3 phosphorylation (p-STAT3) in EGFRT790M and EGFRC797S tumoral cells. Interestingly, we also found that concomitant Notch inhibition with gefitinib or osimertinib treatment induced a p-STAT3-dependent strong reduction in the levels of the transcriptional repressor HES1. Importantly, we showed that tyrosine kinase inhibitor-resistant tumors, with EGFRT790M and EGFRC797S mutations, were highly responsive to the combined treatment of Notch inhibitors with gefitinib or osimertinib, respectively. Finally, in patients with EGFR mutations treated with tyrosine kinase inhibitors, HES1 protein levels increased during relapse and correlated with shorter progression-free survival. Therefore, our results offer a proof of concept for an alternative treatment to chemotherapy in lung adenocarcinoma osimertinib-treated patients after disease progression.
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