{
  "abstract": "Hepatocellular carcinoma (HCC) is the second leading cause of cancer death worldwide, largely due to the limited efficacy of current therapies in advanced stages of the disease. Most cases of HCC develop in the setting of chronic liver disease, particularly cirrhosis, where ongoing cycles of inflammation, hepatocyte death and regeneration foster the gradual accumulation of genetic and epigenetic alterations that promote malignant transformation. These molecular changes contribute to the high degree of tumour heterogeneity observed in HCC, a major factor underlying resistance to current treatments. As a result, sustained clinical responses to existing therapies, such as tyrosine kinase inhibitors, anti-angiogenic agents and immune checkpoint inhibitors, remain uncommon. In this context, a growing body of evidence has identified epigenetic dysregulation as a key driver of tumour progression and therapeutic resistance, highlighting a new frontier for intervention. This review provides clinicians and researchers with a comprehensive overview of the emerging field of epigenetic therapies in HCC, summarising results from both completed and ongoing clinical trials involving the so-called ‘epidrugs’. Importantly, we discuss how targeting epigenetic mechanisms may not only suppress tumour growth but also enhance the effectiveness of current therapies by reversing resistance pathways. By translating complex molecular insights into tangible therapeutic strategies, epigenetics is poised to reshape the future of HCC management, offering renewed hope for more durable and personalised treatment responses in a disease where progress is urgently needed.",
  "authors": [
    {
      "affiliations": [
        "Hepatology and Gene Therapy Program, Instituto de Investigaciones en Medicina Traslacional, CONICET – Universidad Austral, Pilar, Buenos Aires, Argentina",
        "Facultad de Ciencias Biomédicas, Universidad Austral, Pilar, Buenos Aires, Argentina",
        "HZ4 Liver Inc/Spectrum, Dover, Delaware, USA"
      ],
      "name": "Barbara Bueloni"
    },
    {
      "affiliations": [
        "Hepatology Laboratory, Solid Tumors Program, CIMA, CCUN, University of Navarra, Pamplona, Navarra, Spain",
        "Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBER-EHD), Madrid, Spain"
      ],
      "name": "Maite G Fernandez-Barrena"
    },
    {
      "affiliations": [
        "Hepatology and Gene Therapy Program, Instituto de Investigaciones en Medicina Traslacional, CONICET – Universidad Austral, Pilar, Buenos Aires, Argentina",
        "Facultad de Ciencias Biomédicas, Universidad Austral, Pilar, Buenos Aires, Argentina"
      ],
      "name": "Esteban Fiore"
    },
    {
      "affiliations": [
        "Hepatology Laboratory, Solid Tumors Program, CIMA, CCUN, University of Navarra, Pamplona, Navarra, Spain",
        "Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBER-EHD), Madrid, Spain",
        "Instituto de Investigación Sanitaria de Navarra (IdisNA), Pamplona, Navarra, Spain"
      ],
      "name": "Matias A Avila"
    },
    {
      "affiliations": [
        "Hepatology and Gene Therapy Program, Instituto de Investigaciones en Medicina Traslacional, CONICET – Universidad Austral, Pilar, Buenos Aires, Argentina",
        "Facultad de Ciencias Biomédicas, Universidad Austral, Pilar, Buenos Aires, Argentina"
      ],
      "name": "Juan Bayo"
    },
    {
      "affiliations": [
        "Hepatology and Gene Therapy Program, Instituto de Investigaciones en Medicina Traslacional, CONICET – Universidad Austral, Pilar, Buenos Aires, Argentina",
        "Facultad de Ciencias Biomédicas, Universidad Austral, Pilar, Buenos Aires, Argentina",
        "Liver Unit, Hospital Universitario Austral, Universidad Austral, Pilar, Argentina"
      ],
      "name": "Guillermo D Mazzolini"
    }
  ],
  "title": "Epigenetic therapies in hepatocellular carcinoma: emerging clinical tools and applications",
  "uid": "932fca60-326b-58ed-b7df-299a8d80a628"
}