ArticleScientific reports2022
AXL/CDCP1/SRC axis confers acquired resistance to osimertinib in lung cancer.
Article in Scientific reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 22 citations in OpenAlex.
- AXL at the nexus of therapeutic resistance, tumor vascularization, and immune evasion in cancer.iScience · 2026Review
- Article
- A three-gene signature correlated with MAPK/ERK activation characterizes acquired resistance to EGFR-tyrosine kinase inhibitors in non-small cell lung cancer.Oncology letters · 2026Article
- Osimertinib Resistance in EGFR-Mutated Non-Small Cell Lung Cancer: Mechanisms and Therapeutic Strategies.MedComm · 2026Review
- Review
- TRIM26-mediated NKRF degradation drives Osimertinib resistance through SNRPD2-dependent stress granule formation in lung adenocarcinoma.Cell death & disease · 2026Article
- Extracellular vesicle-derived CDCP1 promotes chemoresistance and macrophage polarization in breast cancer.Human cell · 2026Article
- A Multikinase Inhibitor AX-0085 Blocks FGFR1 Activation to Overcomes Osimertinib Resistance in Non-Small Cell Lung Cancer.Biomedicines · 2025Article
- Differential Efficacy of Bevacizumab and Erlotinib in Preclinical Models of Renal Medullary Carcinoma and Fumarate Hydratase-Deficient Renal Cell Carcinoma.Molecular cancer therapeutics · 2025Article
- Differential Role of CD318 in Tumor Immunity Affecting Prognosis in Colorectal Cancer Compared to Other Adenocarcinomas.Journal of clinical medicine · 2025Article
- AXL signaling in cancer: from molecular insights to targeted therapies.Signal transduction and targeted therapy · 2025Review
- The changing treatment landscape of EGFR-mutant non-small-cell lung cancer.Nature reviews. Clinical oncology · 2025Review
- Synergistic Inhibition of Drug Resistant KRAS Mutant Non-Small Cell Lung Cancer by Co-Targeting AXL and SRC.Cancers · 2025Article
- The MET Oncogene Network of Interacting Cell Surface Proteins.International journal of molecular sciences · 2024Review
- Aberrant expression of MRAS and HEG1 as the biomarkers for osimertinib resistance in LUAD.Discover oncology · 2024Article
- Drug tolerant persister cell plasticity in cancer: A revolutionary strategy for more effective anticancer therapies.Signal transduction and targeted therapy · 2024Review
- SOS2 modulates the threshold of EGFR signaling to regulate osimertinib efficacy and resistance in lung adenocarcinoma.Molecular oncology · 2024Article
- Article
- Overexpression of SERPINA3 suppresses tumor progression by modulating SPOP/NF‑κB in lung cancer.International journal of oncology · 2023Article
- AXL in cancer: a modulator of drug resistance and therapeutic target.Journal of experimental & clinical cancer research : CR · 2023Review
Corrections and comments
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Authors and funding
9 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Osimertinib, a third-generation EGFR-TKI, has nowadays been applied to non-small cell lung cancer harboring activated EGFR mutation with or without T790M, but ultimately develop resistance to this drug. Here we report a novel mechanism of acquired resistance to osimertinib and the reversal of which could improve the clinical outcomes. In osimertinib-resistant lung cancer cell lines harboring T790M mutation that we established, expression of multiple EGFR family proteins and MET was markedly reduced, whereas expression of AXL, CDCP1 and SRC was augmented along with activation of AKT. Surprisingly, AXL or CDCP1 expression was induced by osimertinib in a time-dependent manner up to 3 months. Silencing of CDCP1 or AXL restored the sensitivity to osimertinib with reduced activation of SRC and AKT. Furthermore, silencing of both CDCP1 and AXL increased the sensitivity to osimertinib. Either silencing of SRC or dasatinib, a SRC family kinase (SFK) inhibitor, suppressed AKT phosphorylation and cell growth. Increased expression of AXL and CDCP1 was observed in refractory tumor samples from patients with lung cancer treated with osimertinib. Together, this study suggests that AXL/SFK/AKT and CDCP1/SFK/AKT signaling pathways play some roles in acquired osimertinib resistance of non-small cell lung cancer.
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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.