ArticleYonsei medical journal2017
EGF Induced RET Inhibitor Resistance in CCDC6-RET Lung Cancer Cells.
Article in Yonsei medical journal, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 38 citations in OpenAlex.
- Safety, pharmacokinetics and efficacy of HA121-28 in patients with advanced solid tumors and RET fusion-positive non-small-cell lung cancer: a multicenter, open-label, single-arm phase 1/2 trial.Signal transduction and targeted therapy · 2025Trial
- RET Signaling Pathway in Human Cancer: Oncogenic Mechanisms, Selective Inhibitors, and Emerging Resistance Strategies.International journal of molecular sciences · 2026Review
- Oligoprogression in NSCLC with Other Actionable Oncogenic Drivers Beyond EGFR and ALK: An Emerging Entity.International journal of molecular sciences · 2026Review
- Systemic Therapies for Advanced Medullary Thyroid Carcinoma.Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer · 2025Review
- Molecular genetics, therapeutics and RET inhibitor resistance for medullary thyroid carcinoma and future perspectives.Cell communication and signaling : CCS · 2024Review
- Review
- Article
- Drug repositioning in thyroid cancer: from point mutations to gene fusions.Frontiers in oncology · 2024Review
- The heterogeneous transition state of resistance to RET kinase inhibitors converges on ERK1/2-driven Aurora A/B kinases.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2023Article
- Treatment of Advanced Non-Small Cell Lung Cancer with RET Fusions: Reality and Hopes.International journal of molecular sciences · 2023Review
- RET kinase inhibitors forTherapeutic advances in medical oncology · 2022Review
- Review
- Clinicopathologic features of kinase fusion-related thyroid carcinomas: an integrative analysis with molecular characterization.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2020Article
- State-of-the-Art Strategies for TargetingJournal of clinical oncology : official journal of the American Society of Clinical Oncology · 2020Review
- Advances in Targeting RET-Dependent Cancers.Cancer discovery · 2020Review
- Bioinformatics analysis of microRNA expression between patients with and without latent tuberculosis infections.Experimental and therapeutic medicine · 2019Article
- Molecular mechanisms and pathobiology of oncogenic fusion transcripts in epithelial tumors.Oncotarget · 2019Review
- Systematic analysis of NLMP suggests nuclear localization of RTK/MET kinases resemble cancer cell clearance.Journal of experimental & clinical cancer research : CR · 2019Article
- Targeting RET-rearranged non-small-cell lung cancer: future prospects.Lung Cancer (Auckland, N.Z.) · 2019Review
- Genomic Profiling on an Unselected Solid Tumor Population Reveals a Highly Mutated Wnt/β-Catenin Pathway Associated with Oncogenic EGFR Mutations.Journal of personalized medicine · 2018Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeRearrangement of the proto-oncogene rearranged during transfection (RET) has been newly identified potential driver mutation in lung adenocarcinoma. Clinically available tyrosine kinase inhibitors (TKIs) target RET kinase activity, which suggests that patients with RET fusion genes may be treatable with a kinase inhibitor. Nevertheless, the mechanisms of resistance to these agents remain largely unknown. Thus, the present study aimed to determine whether epidermal growth factor (EGF) and hepatocyte growth factor (HGF) trigger RET inhibitor resistance in LC-2/ad cells with CCDC6-RET fusion genes. MATERIALS AND
methodsThe effects of EGF and HGF on the susceptibility of a CCDC6-RET lung cancer cell line to RET inhibitors (sunitinib, E7080, vandetanib, and sorafenib) were examined.
resultsCCDC6-RET lung cancer cells were highly sensitive to RET inhibitors. EGF activated epidermal growth factor receptor (EGFR) and triggered resistance to sunitinib, E7080, vandetanib, and sorafenib by transducing bypass survival signaling through ERK and AKT. Reversible EGFR-TKI (gefitinib) resensitized cancer cells to RET inhibitors, even in the presence of EGF. Endothelial cells, which are known to produce EGF, decreased the sensitivity of CCDC6-RET lung cancer cells to RET inhibitors, an effect that was inhibited by EGFR small interfering RNA (siRNA), anti-EGFR antibody (cetuximab), and EGFR-TKI (Iressa). HGF had relatively little effect on the sensitivity to RET inhibitors.
conclusionEGF could trigger resistance to RET inhibition in CCDC6-RET lung cancer cells, and endothelial cells may confer resistance to RET inhibitors by EGF. E7080 and other RET inhibitors may provide therapeutic benefits in the treatment of RET-positive lung cancer patients.
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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.