ArticleCell death & disease2020
Metformin reduces HGF-induced resistance to alectinib via the inhibition of Gab1.
Article in Cell death & disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 28 citations in OpenAlex.
- Three decades of anaplastic lymphoma kinase: from physiological roles to cancer and immune evasion.Cancer metastasis reviews · 2026Review
- ALK rearrangements and resistance mutations in non-small cell lung cancer: molecular mechanisms and therapeutic implications.Cancer chemotherapy and pharmacology · 2026Review
- Deciphering molecular pathways in urological cancers: A gateway to precision therapeutics.Journal of advanced research · 2026Review
- The therapeutic value of antidiabetic drugs in lung cancer treatment: from clinical evidence to possible mechanisms.Frontiers in immunology · 2026Review
- miR-3606-3p alleviates skin fibrosis by integratively suppressing the integrin/FAK, p-AKT/p-ERK, and TGF-β signaling cascades.Journal of advanced research · 2025Article
- SPANXB1 drives brain metastasis in breast cancer via MMP1 regulation: potential therapeutic insights with metformin.Cell death discovery · 2025Article
- Anti-EGFR therapy can overcome acquired resistance to the third-generation ALK-tyrosine kinase inhibitor lorlatinib mediated by activation of EGFR.Acta pharmacologica Sinica · 2025Article
- Mesenchymal stem cells promote erlotinib resistance in non-small cell lung cancer through the HGF-AKT/ERK1/2-OPN pathway.American journal of translational research · 2025Article
- Mechanisms of Resistance to ALK Inhibitors and Corresponding Treatment Strategies in Lung Cancer.International journal of general medicine · 2025Review
- ALK inhibitors in cancer: mechanisms of resistance and therapeutic management strategies.Cancer drug resistance (Alhambra, Calif.) · 2024Review
- ALK fusions in the pan-cancer setting: another tumor-agnostic target?NPJ precision oncology · 2023Review
- The Role of GAB1 in Cancer.Cancers · 2023Review
- Article
- 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
- Anaplastic lymphoma kinase inhibitors-a review of anticancer properties, clinical efficacy, and resistance mechanisms.Frontiers in pharmacology · 2023Review
- Research progress on the therapeutic effect and mechanism of metformin for lung cancer (Review).Oncology reports · 2023Review
- Protein tyrosine kinase inhibitor resistance in malignant tumors: molecular mechanisms and future perspective.Signal transduction and targeted therapy · 2022Review
- Review
- Molecular mechanisms underlining the role of metformin as a therapeutic agent in lung cancer.Cellular oncology (Dordrecht, Netherlands) · 2021Review
- The Resistance Mechanisms and Treatment Strategies for ALK-Rearranged Non-Small Cell Lung Cancer.Frontiers in oncology · 2021Review
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alectinib is a second-generation anaplastic lymphoma kinase (ALK) inhibitor that has sufficient clinical efficacy and satisfactory safety in ALK-positive non-small cell lung cancer (NSCLC) patients with or without brain metastasis. Alectinib has now become an important drug in the first-line treatment of advanced ALK-positive NSCLC; however, resistance is almost inevitable. The increased expression of hepatocyte growth factor (HGF) and its physiological receptor tyrosine kinase MET have been shown to be linked to acquired resistance to various tyrosine kinase inhibitors (TKIs), and this phenomenon has been observed in some ALK-positive NSCLC tumour tissues. In this study, we found that HGF levels in the culture supernatant of an ALK-positive cell line tended to increase with time and could be further increased by alectinib in a time-dependent manner. Exogenous or endogenous HGF did not cause resistance to the ALK/MET double-targeted small molecule inhibitor crizotinib, but it was an important cause of alectinib resistance. Furthermore, Gab1 was a key effector in the HGF/MET signal transduction pathway that mediated alectinib resistance. The antidiabetic drug metformin combined with alectinib overcame alectinib resistance triggered by HGF/MET through disrupting the complex between MET and Gab1, thereby inhibiting Gab1 phosphorylation and the activation of downstream signal transduction pathways. These results suggest that metformin combined with alectinib may be useful for overcoming alectinib resistance induced by the activation of the HGF/MET signalling pathway and improving the efficacy of alectinib.
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