ArticleThe Journal of clinical investigation2022
MERTK activation drives osimertinib resistance in EGFR-mutant non-small cell lung cancer.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
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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
33 citing papers in PubMed, 44 citations in OpenAlex.
- Fc-Dependent Targeting of the GAS6-MERTK Axis With Monoclonal and Bispecific Antibodies Overcomes Drug Resistance Across EGFR Mutations in Exons 19, 20, and 21.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Interpretable habitat radiomics based nomogram for predicting T790M mutation in non-small cell lung cancer with brain metastases.Quantitative imaging in medicine and surgery · 2026Article
- Review
- MerTK inhibition by UNC569 triggers DNA damage and JNK/p38 MAPK cascade-driven apoptosis in pancreatic cancer.Acta biochimica et biophysica Sinica · 2026Article
- Genetic Association Between Rheumatoid Arthritis and Preeclampsia: A Bidirectional Mendelian Randomization and Bioinformatics Study.Maternal-fetal medicine (Wolters Kluwer Health, Inc.) · 2026Article
- Dysregulation of the ubiquitin-proteasome system in von Hippel-Lindau syndrome: molecular insights and clinical perspectives.Clinical and experimental medicine · 2025Review
- Role of signaling pathways in lung cancer development and advances in targeted therapies (Review).Oncology letters · 2025Review
- From pathogenesis to therapeutic targeting: new insight into TAM receptors in rheumatoid arthritis.Cell & bioscience · 2025Review
- Enhancing Chemosensitivity With Quercetin: Mechanistic Insights Into MerTK and Associated Signaling Pathways.Cancer reports (Hoboken, N.J.) · 2025Review
- [Integrative Analysis of Multi-source Public Databases to Screen Core Genes for Constructing A Prognostic Risk Model in Lung Adenocarcinoma].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2025Article
- MertkImmunity, inflammation and disease · 2025Article
- Discovery of Novel 2-Substituted Aniline Pyrimidine Based Derivatives as Potent Mer/c-Met Dual Inhibitors with Improvement Bioavailability.Biomolecules · 2025Article
- Nuclear pore complex protein RANBP2 and related SUMOylation in solid malignancies.Genes & diseases · 2025Review
- Structure-Based Design of Potent and Selective MerTK Inhibitors by Modulating the Conformation of αC Helix.Journal of medicinal chemistry · 2025Article
- Genome-wide CRISPR-Cas9 screening identifies ITGA8 responsible for abivertinib sensitivity in lung adenocarcinoma.Acta pharmacologica Sinica · 2025Article
- AXL-Mediated Drug Resistance in ALK-Rearranged NSCLC Enhanced by GAS6 From Macrophages and MMP11 Positive Fibroblasts.Cancer science · 2025Article
- Garcinone C inhibits pseudorabies virus replication through EGF/PI3K/Akt axis.Frontiers in cellular and infection microbiology · 2025Article
- CCDC34 maintains stemness phenotype through β-catenin-mediated autophagy and promotes EGFR-TKI resistance in lung adenocarcinoma.Cancer gene therapy · 2025Article
- Abnormally Activated MNX1 Promotes Tumor Growth and Osimertinib Resistance and Predicts Survival in EGFR-Mutant Lung Adenocarcinoma.Drug design, development and therapy · 2025Article
- MerTKScience advances · 2024Article
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
Abstract
Acquired resistance is inevitable in non-small cell lung cancers (NSCLCs) treated with osimertinib (OSI), and the mechanisms are not well defined. The MERTK ligand GAS6 promoted downstream oncogenic signaling in EGFR-mutated (EGFRMT) NSCLC cells treated with OSI, suggesting a role for MERTK activation in OSI resistance. Indeed, treatment with MRX-2843, a first-in-class MERTK kinase inhibitor, resensitized GAS6-treated NSCLC cells to OSI. Both GAS6 and EGF stimulated downstream PI3K/AKT and MAPK/ERK signaling in parental cells, but only GAS6 activated these pathways in OSI-resistant (OSIR) derivative cell lines. Functionally, OSIR cells were more sensitive to MRX-2843 than parental cells, suggesting acquired dependence on MERTK signaling. Furthermore, MERTK and/or its ligands were dramatically upregulated in EGFRMT tumors after treatment with OSI in both xenograft models and patient samples, consistent with induction of autocrine/paracrine MERTK activation. Moreover, treatment with MRX-2843 in combination with OSI, but not OSI alone, provided durable suppression of tumor growth in vivo, even after treatment was stopped. These data identify MERTK as a driver of bypass signaling in treatment-naive and EGFRMT-OSIR NSCLC cells and predict that MRX-2843 and OSI combination therapy will provide clinical benefit in patients with EGFRMT NSCLC.
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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.