ArticleJournal of translational medicine2022
RET fusions as primary oncogenic drivers and secondary acquired resistance to EGFR tyrosine kinase inhibitors in patients with non-small-cell lung cancer.
Article in Journal of translational medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 20 citations in OpenAlex.
- Molecular Characterisations and the Association with Clinical Factors inCancer management and research · 2026Article
- Research progress of small molecule targeted drugs for non-small cell lung cancer.Frontiers in oncology · 2026Review
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- Characterization ofTranslational lung cancer research · 2025Article
- Molecular characteristics and responses to EGFR tyrosine kinase inhibitors in non-small cell lung cancer patients with EGFR exon 19 insertions.BMC medicine · 2025Article
- Targeting the Tumor Microenvironment in EGFR-Mutant Lung Cancer: Opportunities and Challenges.Biomedicines · 2025Review
- Hepatocellular carcinoma: signaling pathways and therapeutic advances.Signal transduction and targeted therapy · 2025Review
- Article
- Mechanisms of resistance to RET-directed therapies.Endocrine-related cancer · 2025Review
- Article
- NTRK1-fusion as an acquired resistance mechanism in EGFRex19 mutated NSCLC: a case report.Frontiers in pharmacology · 2025Article
- Article
- Cabozantinib Response in a Patient With NSCLC Harboring Both MET Exon 14 Skipping Mutation and Secondary RET Fusion: A Case Report.JTO clinical and research reports · 2024Article
- Characteristics and Survival Outcomes of Patients With MetastaticJCO precision oncology · 2024Article
- Clinical advances in EGFR-TKI combination therapy for EGFR-mutated NSCLC: a narrative review.Translational cancer research · 2023Review
- Decoding Oncofusions: Unveiling Mechanisms, Clinical Impact, and Prospects for Personalized Cancer Therapies.Cancers · 2023Review
- Progress and challenges in RET-targeted cancer therapy.Frontiers of medicine · 2023Review
- Treatment of advanced non-small cell lung cancer with driver mutations: current applications and future directions.Frontiers of medicine · 2023Review
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundRET fusions are rare oncogenic drivers in non-small cell lung cancer (NSCLC). While activating RET rearrangements are found in NSCLC patients harboring epidermal growth factor receptor (EGFR) genetic alterations at resistance to EGFR inhibitors, the extent to which co-occurring genomic alterations exist and how they might affect prognosis or therapy response is poorly understood.
methodsTargeted next-generation sequencing (NGS) was used to assess 380 baseline patients with primary RET fusions and 71 EGFR-mutated NSCLC patients who acquired RET fusions after developing resistance to EGFR-tyrosine kinase inhibitors (EGFR-TKIs).
resultsPrimary RET fusions were more likely associated with females and younger age, with KIF5B being the predominant fusion partner. In baseline patients, both SMAD4 (5.3% vs. 0.0%, P = 0.044) and MYC copy-number gain variants (6.9% vs. 0.0%, P = 0.009) were more frequently co-mutated with KIF5B-RET than CCDC6-RET. By contrast, CDKN2A (11.3% vs. 2.4%, P = 0.003) mutations were significantly enriched in CCDC6-RET-rearranged baseline patients. A significant increase in the proportion of CCDC6-RET was observed in acquired RET-rearranged patients (47.3% vs. 22.5%, P < 0.001). The median progression-free survival (PFS) of patients harboring RB1 and TP53 double-mutations (5.5 vs. 10.0 months, P = 0.020) or ERBB2 amplification (5.6 vs. 10.0 months, P = 0.041) was significantly shorter than the wild-type counterparts. Moreover, we identified that RET fusions were more likely associated with acquired resistance (AR) to third-generation EGFR-TKIs than previous generations of EGFR-TKIs.
conclusionsIn conclusion, we depicted the mutational profiles of NSCLC patients who harbor RET fusions at baseline or after resistance to EGFR-TKIs. Furthermore, our results suggest that RET fusions mediate secondary resistance to third-generation EGFR-TKIs and might be associated with poor prognosis in patients with NSCLC.
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