ArticleEBioMedicine2016
P-glycoprotein Mediates Ceritinib Resistance in Anaplastic Lymphoma Kinase-rearranged Non-small Cell Lung Cancer.
Article in EBioMedicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers, 2 of them syntheses that pooled it.
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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
83 citing papers in PubMed, 2 syntheses or guidelines pooled it, 139 citations in OpenAlex.
- Efficacy and safety of anaplastic lymphoma kinase inhibitors for non-small cell lung cancer: A systematic review and network meta-analysis.Thoracic cancer · 2023Pooled it
- Comparative efficacy and safety of first-line treatments for advanced non-small cell lung cancer with ALK-rearranged: a meta-analysis of clinical trials.BMC cancer · 2021Pooled it
- First-Line Lorlatinib in Striatin-Anaplastic Lymphoma Kinase-Positive Lung Adenocarcinoma: A Case Report and Literature Review.Respirology case reports · 2026Article
- Three decades of anaplastic lymphoma kinase: from physiological roles to cancer and immune evasion.Cancer metastasis reviews · 2026Review
- Review
- Molecular Analysis of EBUS-TBNA Samples for Nodal Staging in Non-Small Cell Lung Cancer.Cancers · 2026Review
- Insights and perspectives into the etiology of TKI-induced cardiotoxicity.ASPET discovery · 2026Article
- Refining Criteria for Choosing the First-Line Treatment for Real-World Patients with AdvancedInternational journal of molecular sciences · 2025Review
- Canonical and noncanonical NOTCH signaling in the nongenetic resistance of cancer: distinct and concerted control.Frontiers of medicine · 2025Review
- Mechanisms of Resistance to ALK Inhibitors and Corresponding Treatment Strategies in Lung Cancer.International journal of general medicine · 2025Review
- The Use of Anaplastic Lymphoma Kinase Inhibitors in Non-Small-Cell Lung Cancer Treatment-Literature Review.Biomedicines · 2024Review
- Overcoming ABCB1 mediated multidrug resistance in castration resistant prostate cancer.Cell death & disease · 2024Article
- Overcoming ABCB1 mediated multidrug resistance in castration resistant prostate cancer.Research square · 2024Article
- ALK inhibitors in cancer: mechanisms of resistance and therapeutic management strategies.Cancer drug resistance (Alhambra, Calif.) · 2024Review
- MIG6 loss confers resistance to ALK/ROS1 inhibitors in NSCLC through EGFR activation by low-dose EGF.JCI insight · 2023Article
- Successful Treatment with Crizotinib to Overcome Drug Resistance Possibly Due to Mesenchymal-epithelial Transition Amplification in a Lung Cancer Patient with the Echinoderm Microtubule-associated Protein-like 4-anaplastic Lymphoma Kinase Fusion Gene.Internal medicine (Tokyo, Japan) · 2023Article
- [Drug Resistance Mechanism and Therapeutic Strategy of Targeted Therapy of Non-small Cell Lung Cancer with MET Alterations].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2023Article
- β-Sitosterol as a Promising Anticancer Agent for Chemoprevention and Chemotherapy: Mechanisms of Action and Future Prospects.Advances in nutrition (Bethesda, Md.) · 2023Review
- Anaplastic lymphoma kinase inhibitor development: enhanced delivery to the central nervous system.Translational lung cancer research · 2023Article
- Integration of Multi-omic Data in a Molecular Tumor Board Reveals EGFR-Associated ALK-Inhibitor Resistance in a Patient With Inflammatory Myofibroblastic Cancer.The oncologist · 2023Article
23 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The anaplastic lymphoma kinase (ALK) fusion oncogene is observed in 3%-5% of non-small cell lung cancer (NSCLC). Crizotinib and ceritinib, a next-generation ALK tyrosine kinase inhibitor (TKI) active against crizotinib-refractory patients, are clinically available for the treatment of ALK-rearranged NSCLC patients, and multiple next-generation ALK-TKIs are currently under clinical evaluation. These ALK-TKIs exhibit robust clinical activity in ALK-rearranged NSCLC patients; however, the emergence of ALK-TKI resistance restricts the therapeutic effect. To date, various secondary mutations or bypass pathway activation-mediated resistance have been identified, but large parts of the resistance mechanism are yet to be identified. Here, we report the discovery of p-glycoprotein (P-gp/ABCB1) overexpression as a ceritinib resistance mechanism in ALK-rearranged NSCLC patients. P-gp exported ceritinib and its overexpression conferred ceritinib and crizotinib resistance, but not to PF-06463922 or alectinib, which are next-generation ALK inhibitors. Knockdown of ABCB1 or P-gp inhibitors sensitizes the patient-derived cancer cells to ceritinib, in vitro and in vivo. P-gp overexpression was identified in three out of 11 cases with in ALK-rearranged crizotinib or ceritinib resistant NSCLC patients. Our study suggests that alectinib, PF-06463922, or P-gp inhibitor with ceritinib could overcome the ceritinib or crizotinib resistance mediated by P-gp overexpression.
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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.