ArticleNPJ precision oncology2022
HER3 activation contributes toward the emergence of ALK inhibitor-tolerant cells in ALK-rearranged lung cancer with mesenchymal features.
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 19 papers.
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Who cites it
19 citing papers in PubMed, 24 citations in OpenAlex.
- AXL-SHC1 signaling axis mediates adaptive resistance to HER2-targeted tyrosine kinase inhibitors in HER2-aberrant lung and gastric cancers.NPJ precision oncology · 2026Article
- Lorlatinib in ALK-positive non-small cell lung cancer: final survival data that reshape the therapeutic landscape.Translational lung cancer research · 2025Article
- Utility of serum CYFRA 21-1 as a prognostic biomarker in ALK-positive non-small cell lung cancer treated with ALK-TKIs: a retrospective cohort study.Translational lung cancer research · 2025Article
- 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
- Targeting ERBB3 and AKT to overcome adaptive resistance in EML4-ALK-driven non-small cell lung cancer.Cell death & disease · 2024Article
- Targeting ErbB and tankyrase1/2 prevent the emergence of drug-tolerant persister cells in ALK-positive lung cancer.NPJ precision oncology · 2024Article
- Review
- Targeting of drug-tolerant persister cells as an approach to counter drug resistance in non-small cell lung cancer.Lung cancer (Amsterdam, Netherlands) · 2024Review
- Farnesyltransferase inhibition overcomes oncogene-addicted non-small cell lung cancer adaptive resistance to targeted therapies.Nature communications · 2024Article
- HER3 overexpression: a predictive marker for poor prognosis in advanced ALK-positive non-small cell lung cancer treated with ALK inhibitors.Translational lung cancer research · 2024Article
- Role of human epidermal growth factor receptor 3 in treatment resistance of anaplastic lymphoma kinase translocated non-small cell lung cancer.Cancer biology & therapy · 2023Article
- MIG6 loss confers resistance to ALK/ROS1 inhibitors in NSCLC through EGFR activation by low-dose EGF.JCI insight · 2023Article
- FGFR blockade inhibits targeted therapy-tolerant persister in basal FGFR1- and FGF2-high cancers with driver oncogenes.NPJ precision oncology · 2023Article
- Targeting drug-tolerant cells: A promising strategy for overcoming acquired drug resistance in cancer cells.MedComm · 2023Review
- Yes-associated protein 1 mediates initial cell survival during lorlatinib treatment through AKT signaling in ROS1-rearranged lung cancer.Cancer science · 2023Article
- Adaptive resistance to lorlatinib via EGFR signaling in ALK-rearranged lung cancer.NPJ precision oncology · 2023Article
- Targeting HER3 to overcome EGFR TKI resistance in NSCLC.Frontiers in immunology · 2023Review
- Pan-HER inhibitors overcome lorlatinib resistance caused by NRG1/HER3 activation in ALK-rearranged lung cancer.Cancer science · 2023Article
- Review
Corrections and comments
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Authors and funding
25 authors at 9 institutions in 1 country.
Funding
Abstract
Anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKIs) have shown dramatic efficacy in patients with ALK-rearranged lung cancer; however, complete response in these patients is rare. Here, we investigated the molecular mechanisms underlying the emergence and maintenance of drug-tolerant cells in ALK-rearranged lung cancer. Cell based-assays demonstrated that HER3 activation and mesenchymal-to-epithelial transition, mediated through ZEB1 proteins, help maintain cell survival and induce the emergence of ALK-TKI-tolerant cells. Compared with ALK-TKIs alone, cotreatment with pan-HER inhibitor afatinib and ALK-TKIs prevented tumor regrowth, leading to the eradication of tumors in ALK-rearranged tumors with mesenchymal features. Moreover, pre-treatment vimentin expression in clinical specimens obtained from patients with ALK-rearranged lung cancer was associated with poor ALK-TKI treatment outcomes. These results demonstrated that HER3 activation plays a pivotal role in the emergence of ALK-TKI-tolerant cells. Furthermore, the inhibition of HER3 signals combined with ALK-TKIs dramatically improves treatment outcomes for ALK-rearranged lung cancer with mesenchymal features.
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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.