ArticleCancer science2017
Amphiregulin triggered epidermal growth factor receptor activation confers in vivo crizotinib-resistance of EML4-ALK lung cancer and circumvention by epidermal growth factor receptor inhibitors.
Article in Cancer science, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 33 citations in OpenAlex.
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- CircSPINT2 confers sensitivity to osimertinib via hsa-miR-1296-3p/RBP1 axis and inhibits NSCLC progression.Molecular therapy. Oncology · 2025Article
- Laminin-γ2-NR6A1 Fusion Protein Promotes Metastatic Potential in Non-Small-Cell Lung Carcinoma Cells without Epidermal Growth Factor Receptor Mutation.The American journal of pathology · 2025Article
- Coregulatory effects of multiple histone modifications in key ferroptosis-related genes for lung adenocarcinoma.Epigenomics · 2024Article
- Prospective observational study to explore genes and proteins predicting efficacy and safety of brigatinib for ALK-gene rearranged non-small-cell lung cancer: study protocol for ABRAID study (WJOG11919L).Therapeutic advances in medical oncology · 2024Article
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- Single-Cell Characterization of Pulmonary Nodules Implicates Suppression of Immunosurveillance across Early Stages of Lung Adenocarcinoma.Cancer research · 2023Article
- An insight into lung cancer: a comprehensive review exploring ALK TKI and mechanisms of resistance.Bosnian journal of basic medical sciences · 2022Review
- Trametinib overcomes KRAS-G12V-induced osimertinib resistance in a leptomeningeal carcinomatosis model of EGFR-mutant lung cancer.Cancer science · 2021Article
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- Glycogen synthase kinase-3 inhibition overcomes epithelial-mesenchymal transition-associated resistance to osimertinib in EGFR-mutant lung cancer.Cancer science · 2020Article
- Anti-EGF antibodies as surrogate biomarkers of clinical efficacy in stage IIIB/IV non-small-cell lung cancer patients treated with an optimized CIMAvax-EGF vaccination schedule.Oncoimmunology · 2020Article
- Epigallocatechin‑3‑gallate modulates long non‑coding RNA and mRNA expression profiles in lung cancer cells.Molecular medicine reports · 2019Article
- Established, emerging and elusive molecular targets in the treatment of lung cancer.The Journal of pathology · 2018Review
- In vivo imaging xenograft models for the evaluation of anti-brain tumor efficacy of targeted drugs.Cancer medicine · 2017Article
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- Characterization of Aurora A and Its Impact on the Effect of Cisplatin-Based Chemotherapy in Patients with Non-Small Cell Lung Cancer.Translational oncology · 2017Article
- Adverse renal effects of anaplastic lymphoma kinase inhibitors and the response to alectinib of an ALK+ lung cancer patient with renal dysfunction.OncoTargets and therapy · 2017Article
- Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Crizotinib, a first-generation anaplastic lymphoma kinase (ALK) tyrosine-kinase inhibitor, is known to be effective against echinoderm microtubule-associated protein-like 4 (EML4)-ALK-positive non-small cell lung cancers. Nonetheless, the tumors subsequently become resistant to crizotinib and recur in almost every case. The mechanism of the acquired resistance needs to be deciphered. In this study, we established crizotinib-resistant cells (A925LPE3-CR) via long-term administration of crizotinib to a mouse model of pleural carcinomatous effusions; this model involved implantation of the A925LPE3 cell line, which harbors the EML4-ALK gene rearrangement. The resistant cells did not have the secondary ALK mutations frequently occurring in crizotinib-resistant cells, and these cells were cross-resistant to alectinib and ceritinib as well. In cell clone #2, which is one of the clones of A925LPE3-CR, crizotinib sensitivity was restored via the inhibition of epidermal growth factor receptor (EGFR) by means of an EGFR tyrosine-kinase inhibitor (erlotinib) or an anti-EGFR antibody (cetuximab) in vitro and in the murine xenograft model. Cell clone #2 did not have an EGFR mutation, but the expression of amphiregulin (AREG), one of EGFR ligands, was significantly increased. A knockdown of AREG with small interfering RNAs restored the sensitivity to crizotinib. These data suggest that overexpression of EGFR ligands such as AREG can cause resistance to crizotinib, and that inhibition of EGFR signaling may be a promising strategy to overcome crizotinib resistance in EML4-ALK lung cancer.
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