ArticleNPJ precision oncology2022
GSK3 inhibition circumvents and overcomes acquired lorlatinib resistance in ALK-rearranged non-small-cell lung cancer.
Article in NPJ precision oncology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 15 citations in OpenAlex.
- ALK-tyrosine kinase inhibitor resistance due to acquiredTranslational lung cancer research · 2026Article
- From bench to bedside: navigating the clinical translation of GSK-3β inhibition in lung cancer.Medical oncology (Northwood, London, England) · 2025Article
- Harnessing GSK-3β inhibition for lung cancer therapy: emerging opportunities and challenges.Medical oncology (Northwood, London, England) · 2025Review
- Article
- Combined blockade of GPX4 and activated EGFR/HER3 bypass pathways inhibits the development of ALK-inhibitor-induced tolerant persister cells in ALK-fusion-positive lung cancer.Molecular oncology · 2025Article
- Article
- [Crizotinib Treatment for Lorlatinib-resistant MET-amplified EML4-ALK-fusion Positive Advanced Lung Adenocarcinoma: A Case Report].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2024Article
- New findings on the incidence and management of CNS adverse reactions in ALK-positive NSCLC with lorlatinib treatment.Discover oncology · 2024Article
- A Rapid One-Pot Workflow for Sensitive Microscale Phosphoproteomics.Journal of proteome research · 2024Article
- Targeting of drug-tolerant persister cells as an approach to counter drug resistance in non-small cell lung cancer.Lung cancer (Amsterdam, Netherlands) · 2024Review
- MIG6 loss confers resistance to ALK/ROS1 inhibitors in NSCLC through EGFR activation by low-dose EGF.JCI insight · 2023Article
- Comparative Efficacy of ALK Inhibitors for Treatment-Naïve ALK-Positive Advanced Non-Small Cell Lung Cancer with Central Nervous System Metastasis: A Network Meta-Analysis.International journal of molecular sciences · 2023Review
- Fibroblast growth factor receptor 3 overexpression mediates ALK inhibitor resistance in ALK-rearranged non-small cell lung cancer.Cancer science · 2022Article
- Construction and evaluation of a prognostic risk model of tumor metastasis-related genes in patients with non-small cell lung cancer.BMC medical genomics · 2022Article
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
Abstract
Anaplastic lymphoma kinase (ALK) fusion is found in ~3%-5% of patients with non-small-cell lung cancers (NSCLCs). Although the third-generation ALK tyrosine kinase inhibitor (TKI) lorlatinib shows high clinical efficacy in ALK-positive NSCLC, most of the patients eventually relapse with acquired resistance. Recently, drug-tolerant persister (DTP) cells have been considered an important seed of acquired resistance cells. In this study, we established lorlatinib intermediate resistant cells from a patient-derived cell model. Glycogen synthase kinase 3 (GSK3) inhibitions significantly suppressed lorlatinib intermediate resistant cell growth. GSK3 inhibition also sensitized acquired resistance cells derived from alectinib-treated patients with or without secondary mutations to lorlatinib. Therefore, GSK3 plays a crucial role in developing acquired resistance against lorlatinib in ALK-positive NSCLC mediated by lorlatinib intermediate resistant cells and could be a potential molecular target to prevent acquired lorlatinib resistance and overcome ALK-TKI resistance.
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Registered trials
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