ArticleCells2023
Curcumin-Mediated Resistance to Lenvatinib via EGFR Signaling Pathway in Hepatocellular Carcinoma.
Article in Cells, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 33 citations in OpenAlex.
- Efficacy and safety of lenvatinib plus gefitinib in lenvatinib-resistant hepatocellular carcinomas: a prospective, single-arm exploratory trial.Signal transduction and targeted therapy · 2024Trial
- Metabolic Activation-Dependent Anti-Liver Cancer Activity and Organ-Specific Toxicity of Retrorsine From Fanhuncao (Jacobaea cannabifolia and J. litvinovii).Archiv der Pharmazie · 2026Article
- p53-R280S mutation confers lenvatinib resistance in hepatocellular carcinoma via Bcl-2-mediated anti-apoptotic signaling.Molecular and cellular biochemistry · 2026Article
- Nutritional Impact on Breast Cancer in Menopausal and Post-Menopausal Patients Treated with Aromatase Inhibitors.Cancers · 2025Review
- Unraveling the mechanism of curcumin in coronary slow flow phenomenon through network pharmacology and molecular docking.Scientific reports · 2025Article
- Molecular targets and therapeutic implications of curcumin in hepatocellular carcinoma: a comprehensive literature review.Cancer cell international · 2025Review
- Exploring the antitumor effect of curcumin-piperlongumine hybrid molecule (CP) on EGFR-TKI-resistant non-small cell lung cancer using network pharmacological analysis and experimental verification.Acta biochimica et biophysica Sinica · 2025Article
- Natural anti-cancer products: insights from herbal medicine.Chinese medicine · 2025Review
- An aptamer-conjugated mesoporous polydopamine formulation for synergistic targeted and photothermal therapy of hepatocellular carcinoma.International journal of pharmaceutics: X · 2025Article
- Curcumin and Its Derivatives in Hepatology: Therapeutic Potential and Advances in Nanoparticle Formulations.Cancers · 2025Review
- Role of Curcumin in Chronic Liver Diseases: A Comprehensive Review.Drug design, development and therapy · 2025Review
- Lenvatinib and immune-checkpoint inhibitors in hepatocellular carcinoma: mechanistic insights, clinical efficacy, and future perspectives.Journal of hematology & oncology · 2024Review
- The Dynamic Role of Curcumin in Mitigating Human Illnesses: Recent Advances in Therapeutic Applications.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Aronia Berry Extract Modulates MYD88/NF-kB/P-Glycoprotein Axis to Overcome Gemcitabine Resistance in Pancreatic Cancer.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Mechanisms and therapeutic targets of ErbB family receptors in hepatocellular carcinoma: a narrative review.Translational cancer research · 2024Review
- Roles of clinical application of lenvatinib and its resistance mechanism in advanced hepatocellular carcinoma (Review).American journal of cancer research · 2024Review
- Advances in hepatocellular carcinoma drug resistance models.Frontiers in medicine · 2024Review
- Multifunctional roles of inflammation and its causative factors in primary liver cancer: A literature review.World journal of hepatology · 2023Review
- Targeting Oxidative Stress with Polyphenols to Fight Liver Diseases.Antioxidants (Basel, Switzerland) · 2023Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
Lenvatinib is a multi-kinase inhibitor approved as a first-line treatment for patients with unresectable advanced hepatocellular carcinoma (HCC). However, its response rate is unsatisfactory, primarily due to the acquisition of resistance, which limits its clinical significance for treating patients with HCC. Recent evidence suggests that epidermal growth factor receptor (EGFR) activation can trigger Lenvatinib-resistance; and is considered an important therapeutic target in HCC. Curcumin, one of the most studied naturally occurring botanicals with robust anti-cancer activity, is also reported to be a potent tyrosine kinase inhibitor. In this study, we hypothesized that the anti-EGFR potential of Curcumin might help overcome Lenvatinib resistance in HCC. We established two Lenvatinib-resistant cells and discovered that a combination of Curcumin and Lenvatinib exhibited a synergistic anti-tumor efficacy in the resistant HCC cell lines. In line with previous reports, Lenvatinib-resistant cell lines revealed significant activation of the EGFR, and genomewide transcriptomic profiling analysis identified that the PI3K-AKT pathway was associated with Lenvatinib resistance. The combination treatment with Curcumin and Lenvatinib dramatically suppressed gene and protein expression of the EGFR-PI3K-AKT pathway, suggesting Curcumin overcomes Lenvatinib resistance via inhibition of EGFR. We further validated these findings in tumor spheroids derived from resistant cell lines. In conclusion, we, for the first time, report that Curcumin reverses Lenvatinib resistance in HCC, and that their combination has clinical application potential for adjunctive treatment in HCC.
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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.