ArticleInternational journal of biological sciences2024
HDAC Inhibition Sensitize Hepatocellular Carcinoma to Lenvatinib via Suppressing AKT Activation.
Article in International journal of biological sciences, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- Combination of Lenvatinib and Antibiotics: A Potential Approach to Enhance Sensitivity in Differentiated Thyroid Cancer.International journal of cancer · 2026Article
- Mitophagy interacts with mitochondrial dynamics and biogenesis, acting as a double-edged sword in digestive cancer.iScience · 2026Review
- Chromatin chronicles: Unlocking the therapeutic potential of histone modifiers in hepatocellular carcinoma.Medical oncology (Northwood, London, England) · 2026Review
- Targeting Cuproptosis and Ferroptosis via a ROS-Responsive Nanoplatform for Enhanced Synergistic Therapy Against Hepatocellular Carcinoma.Antioxidants (Basel, Switzerland) · 2026Article
- RPRD1A drives lenvatinib resistance in hepatocellular carcinoma via the ITGA5-FAK signaling axis.Molecular biomedicine · 2026Article
- Targeting Inflammation and Immune Regulation in Chronic Inflammation Associated Cancers.Cancer science · 2026Review
- Integrated transcriptomic and single cell analysis combined with artificial neural network identifies a robust gene signature for early discrimination of MASL and MASH.Frontiers in immunology · 2026Article
- Clinical progress and functional modalities of HDAC inhibitor-based combination therapies in cancer treatment.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Single-cell sequencing and organoids: applications in organ development and disease.Molecular biomedicine · 2025Review
- Resistance of first-line targeted drugs in hepatocellular carcinoma: the epigenetic regulation mechanisms.Cell death & disease · 2025Review
- Aberrant activation of the PI3K/AKT/HIF‑1α pathway promotes glycolysis and lenvatinib resistance in liver cancer.Molecular medicine reports · 2025Article
- Dona Flor and her two husbands: Discovery of novel HDAC6/AKT2 inhibitors for myeloid cancer treatment.Computers in biology and medicine · 2025Article
- Review
- Targeted intervention of tumor microenvironment with HDAC inhibitors and their combination therapy strategies.European journal of medical research · 2025Review
- HDAC inhibitor MS275 reprograms metabolism to induce differentiation and suppress proliferation in hepatocellular carcinoma.Frontiers in immunology · 2025Article
- Regulated Cell Death in Lenvatinib Resistance of Hepatocellular Carcinoma: from Molecular Mechanisms to Therapeutic Strategies.International journal of biological sciences · 2025Review
- Diaryl pyrimidine guanidine suppresses hepatocellular carcinoma cell stemness by targeting β-catenin signaling.Frontiers in oncology · 2025Article
- Exosomal circular RNAs in tumor microenvironment: An emphasis on signaling pathways and clinical opportunities.MedComm · 2024Review
- Review
- Organoids and spheroids: advancedFrontiers in cell and developmental biology · 2024Review
Corrections and comments
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatocellular carcinoma (HCC) is a deadly malignancy with limited treatment options. As a first-line treatment for advanced HCC, Lenvatinib has been applicated in clinic since 2018. Resistance to Lenvatinib, however, has severely restricted the clinical benefits of this drug. Therefore, it is urgent to explore the potential resistance mechanisms of Lenvatinib and identify appropriate methods to reduce resistance for the treatment of HCC. We identified SAHA, a HDAC inhibitor, to have effective anti-tumor activity against Lenvatinib-resistant HCC organoids by screening a customized drug library. Mechanism analysis revealed that SAHA upregulates PTEN expression and suppresses AKT signaling, which contributes to reversing Lenvatinib resistance in liver cancer cells. Furthermore, combinational application of Lenvatinib and HDAC inhibitor or AKT inhibitor synergistically inhibits HCC cell proliferation and induces cell apoptosis. Finally, we confirmed the synergistic effects of Lenvatinib and SAHA, or AZD5363 in primary liver cancer patient derived organoids. Collectively, these findings may enable the development of Lenvatinib combination therapies for HCC.
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