ArticleCancer research2021
Alterations in the Global Proteome and Phosphoproteome in Third Generation EGFR TKI Resistance Reveal Drug Targets to Circumvent Resistance.
Article in Cancer research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 63 citations in OpenAlex.
- Review
- Epidermal growth factor receptor tyrosine kinase inhibitor for the treatment of non-small cell lung cancer in the past 30 years (1997-2026).Chinese medical journal · 2026Review
- Nicotinamide N-methyltransferase promotes drug resistance in lung cancer, as revealed by nascent proteomic profiling.Molecular oncology · 2026Article
- Integrative phosphoproteomics reveals kinase-mediated regulation of OCIAD1 and its roles in mitochondrial quality control.Frontiers in bioinformatics · 2026Article
- FN-1501 Synergistically Enhances Almonertinib Efficacy in EGFR-TKI-Resistant Lung Adenocarcinoma through Ferroptosis Induction.Anti-cancer agents in medicinal chemistry · 2026Article
- From EGFR PTM network to TKI resistance: spatial subtypes and targeting in lung cancer.Cancer drug resistance (Alhambra, Calif.) · 2026Review
- MUCIN 1 confers inflammatory memory of tyrosine kinase inhibitor resistance in non-small cell lung cancer.Signal transduction and targeted therapy · 2025Article
- A CMTM6 Nanobody Overcomes EGFR-TKI Resistance in Non-Small Cell Lung Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Strategies Beyond 3rd EGFR-TKI Acquired Resistance: Opportunities and Challenges.Cancer medicine · 2025Review
- RBM15 facilitates osimertinib resistance of lung adenocarcinoma through m6A-dependent epigenetic silencing of SPOCK1.Oncogene · 2025Article
- An "AND" logic gate-based supramolecular therapeutic nanoplatform for combatting drug-resistant non-small cell lung cancer.Science advances · 2024Article
- PrPOncogene · 2024Article
- MUC1-C Is a Common Driver of Acquired Osimertinib Resistance in NSCLC.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2024Article
- Duloxetine enhances the sensitivity of non-small cell lung cancer cells to EGFR inhibitors by REDD1-induced mTORC1/S6K1 suppression.American journal of cancer research · 2024Article
- Diverse perspectives on proteomic posttranslational modifications to address EGFR-TKI resistance in non-small cell lung cancer.Frontiers in cell and developmental biology · 2024Review
- Characterization of circRNAs in established osimertinib‑resistant non‑small cell lung cancer cell lines.International journal of molecular medicine · 2023Article
- 3-Phosphoinositide-dependent kinase 1 drives acquired resistance to osimertinib.Communications biology · 2023Article
- Article
- The Role of Proteomics and Phosphoproteomics in the Discovery of Therapeutic Targets and Biomarkers in Acquired EGFR-TKI-Resistant Non-Small Cell Lung Cancer.International journal of molecular sciences · 2023Review
- Targeting epigenetic regulators to overcome drug resistance in cancers.Signal transduction and targeted therapy · 2023Review
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
Lung cancer is the leading cause of cancer mortality worldwide. The treatment of patients with lung cancer harboring mutant EGFR with orally administered EGFR tyrosine kinase inhibitors (TKI) has been a paradigm shift. Osimertinib and rociletinib are third-generation irreversible EGFR TKIs targeting the EGFR T790M mutation. Osimertinib is the current standard of care for patients with EGFR mutations due to increased efficacy, lower side effects, and enhanced brain penetrance. Unfortunately, all patients develop resistance. Genomic approaches have primarily been used to interrogate resistance mechanisms. Here we characterized the proteome and phosphoproteome of a series of isogenic EGFR-mutant lung adenocarcinoma cell lines that are either sensitive or resistant to these drugs, comprising the most comprehensive proteomic dataset resource to date to investigate third generation EGFR TKI resistance in lung adenocarcinoma. Unbiased global quantitative mass spectrometry uncovered alterations in signaling pathways, revealed a proteomic signature of epithelial-mesenchymal transition, and identified kinases and phosphatases with altered expression and phosphorylation in TKI-resistant cells. Decreased tyrosine phosphorylation of key sites in the phosphatase SHP2 suggests its inhibition, resulting in subsequent inhibition of RAS/MAPK and activation of PI3K/AKT pathways. Anticorrelation analyses of this phosphoproteomic dataset with published drug-induced P100 phosphoproteomic datasets from the Library of Integrated Network-Based Cellular Signatures program predicted drugs with the potential to overcome EGFR TKI resistance. The PI3K/MTOR inhibitor dactolisib in combination with osimertinib overcame resistance both
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