ArticleMedical oncology (Northwood, London, England)2021
Targeting Hedgehog signalling in CD133-positive hepatocellular carcinoma: improving Lenvatinib therapeutic efficiency.
Article in Medical oncology (Northwood, London, England), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 19 citations in OpenAlex.
- ERBB3 blockade sensitizes hepatocellular carcinoma to regorafenib after first-line tyrosine kinase inhibitor resistance by inhibiting HIF1A-ABCB1 signaling.Clinical and molecular hepatology · 2026Article
- Polymeric Nanomedicines for siRNA Delivery in Hepatocellular Carcinoma: Emerging Therapeutic Strategies, Combination Approaches, and Translational Perspectives.International journal of nanomedicine · 2026Review
- FBXO32 ubiquitination of SUFU promotes progression and lenvatinib resistance in hepatocellular carcinoma via hedgehog signaling.Medical oncology (Northwood, London, England) · 2025Article
- Advances in Lipid-Based Nanomedicine: Pathway Specific siRNA Therapy and Optimizing Delivery for Hepatocellular Carcinoma.International journal of nanomedicine · 2025Review
- Exploration of the role of immune cells and cell therapy in hepatocellular carcinoma.Frontiers in immunology · 2025Review
- Lenvatinib and immune-checkpoint inhibitors in hepatocellular carcinoma: mechanistic insights, clinical efficacy, and future perspectives.Journal of hematology & oncology · 2024Review
- Insights into lenvatinib resistance: mechanisms, potential biomarkers, and strategies to enhance sensitivity.Medical oncology (Northwood, London, England) · 2024Review
- Roles of clinical application of lenvatinib and its resistance mechanism in advanced hepatocellular carcinoma (Review).American journal of cancer research · 2024Review
- Evaluation and Application of Drug Resistance by Biomarkers in the Clinical Treatment of Liver Cancer.Cells · 2023Review
- Drug Repurposing Flubendazole to Suppress Tumorigenicity via PCSK9-dependent Inhibition and Potentiate Lenvatinib Therapy for Hepatocellular Carcinoma.International journal of biological sciences · 2023Article
- SGOL2 is a novel prognostic marker and fosters disease progression via a MAD2-mediated pathway in hepatocellular carcinoma.Biomarker research · 2022Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Lenvatinib has been approved as a first-line treatment for advanced hepatocellular carcinoma (HCC) in recent years. However, Lenvatinib resistance hinders its therapeutic effect, and the underlying mechanism of action of Lenvatinib needs to be better understood. Increasing studies have suggested that cancer stem cells (CSCs) are an important driving force. Hedgehog signalling is important for the maintenance of hepatocellular carcinoma stemness. In the present study, we investigated the therapeutic role of the Hedgehog signalling inhibitor in reversing Lenvatinib resistance in CD133-positive HCC cells. First, we examined the inhibitory impact of Lenvatinib against CD133 expression in HCC cell lines through Western blot. The CCK8 assay showed that GANT61, a Hedgehog signalling inhibitor, has a suppression advantage over other CSCs-related signalling inhibitors regarding cell viability. Moreover, Lenvatinib and GANT61 combined had better inhibitory effects on cell viability and malignant properties, both in vivo and in vitro. In addition, GANT61 reversed the upregulation of CD133 and Hedgehog signalling caused by Lenvatinib in SK-Hep-1 and MHCC97H. Thus, our results suggested that GANT61 reversed Lenvatinib resistance by suppressing Hedgehog signalling in HCC cells, especially in CD133-positive cells and combining Lenvatinib with Hedgehog signalling inhibitors could improve its therapeutic efficacy in HCC patients with high CD133 expression levels.
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