ArticleJournal of translational medicine2022
Role of chemokine-mediated angiogenesis in resistance towards crizotinib and its reversal by anlotinib in EML4-ALK positive NSCLC.
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 12 papers.
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12 citing papers in PubMed, 17 citations in OpenAlex.
- Targeting serine synthesis pathway to reverse paclitaxel resistance in NSCLC with combination of paclitaxel and anlotinib.Journal of experimental & clinical cancer research : CR · 2026Article
- Advanced ALK-EML4 fusion-positive non-small cell lung cancer with intraspinal metastases: a case report.Frontiers in oncology · 2026Article
- CCL20 in the tumor microenvironment: implications for cancer progression and therapeutic approaches.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Review
- Off-label use of anlotinib in malignancies' treatment: efficacy and management of adverse reactions.Pharmacological reports : PR · 2025Review
- Nutrients Lowering Obesity-Linked Chemokines Blamable for Metastasis.International journal of molecular sciences · 2025Review
- Feasibility and Safety of Anlotinib Plus Docetaxel versus Docetaxel Monotherapy in Patients with Previously Immunotherapy-Treated NSCLC: A Retrospective Exploratory Study.International journal of general medicine · 2025Article
- A novel prognostic model for lung squamous cell carcinoma based on multi-omics analysis and machine learning.PloS one · 2025Article
- CXCR7 promotes pulmonary vascular remodeling via targeting p38/MMP2 pathway in pulmonary arterial hypertension.Journal of thoracic disease · 2024Article
- Two germline mutations can serve as genetic susceptibility screening makers for a lung adenocarcinoma family.Journal of cancer research and clinical oncology · 2023Article
- Case Report: Long-term remission of malignant pleural and peritoneal effusion in a case of advanced lung adenocarcinoma treated with combined crizotinib and anlotinib therapy.Frontiers in oncology · 2023Article
- Knockdown of NUPR1 inhibits angiogenesis in lung cancer through IRE1/XBP1 and PERK/eIF2α/ATF4 signaling pathways.Open medicine (Warsaw, Poland) · 2023Article
- Emerging role of chemokines in small cell lung cancer: Road signs for metastasis, heterogeneity, and immune response.Seminars in cancer biology · 2022Review
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Authors and funding
8 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundThe identification of early plasma biomarkers for clinical outcomes and drug resistance has key importance for risk stratification in anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC) patients. Moreover, it remains unclear whether the anti-angiogenic drug anlotinib can reverse the resistance of ALK-tyrosine kinase inhibitor (ALK-TKI) crizotinib, and no research has explored the effect of anlotinib combined with crizotinib on ALK-positive patients.
methodsIn this study, 76 baseline and longitudinal plasma samples from 61 ALK-positive NSCLC patients receiving crizotinib treatment were analyzed by Luminex liquid suspension chip for 40 chemokines. RNA sequence (RNA-seq) was used to identify differentially expressed genes (DEGs) between H3122 and H3122-crizotinib resistant (H3122CR) cells. Tube formation assay was performed to investigate the effect of chemokines on angiogenesis. And H3122CR-derived xenograft model was constructed to validate the efficacy and safety of anlotinib combined with crizotinib in vivo.
resultsBaseline and progression plasma samples detection suggested that CCL20 played a crucial role in monitoring and predicting the clinical response of crizotinib (hazard ratio for progression-free survival: 2.27 (1.13-4.58); for overall survival: 2.7 (1.23-5.8)). RNA-seq results for H3122 and H3122CR cells showed that high expression of chemokines and angiogenesis pathways were involved in crizotinib resistance. Subsequently, in vitro experiments indicated that CCL20 may induce crizotinib resistance by activation of angiogenesis via JAK2/STAT3-CCL20-VEGFA/IL6 axis. We further found that anti-angiogenic TKI anlotinib could reverse crizotinib resistance by inhibiting chemokines-induced angiogenesis, and anlotinib combined with crizotinib has a better antitumor effect than monotherapy in vitro & in vivo.
conclusionsOverall, CCL20-mediated angiogenesis is involved in crizotinib resistance and could be overcome by using anlotinib in EML4-ALK positive NSCLC. The combination of anlotinib and crizotinib is a promising strategy for patients resistant to ALK-TKIs.
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