{
  "abstract": "Hepatocellular carcinoma (HCC) is an aggressive malignancy, and most patients are diagnosed at intermediate or advanced stages. Targeted therapies, immunotherapies, and combination regimens have limited efficacy, creating a major clinical challenge. The phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway is frequently and persistently activated in HCC. Epigenetic modifications regulate gene expression without altering the DNA sequence and contribute to malignant progression. Aberrant epigenetic states sustain PI3K/AKT activation by silencing tumor-suppressor genes and activating oncogenic signaling. Conversely, activated PI3K/AKT signaling remodels the epigenome through several enzymes that mediate epigenetic modifications. This bidirectional interaction promotes HCC progression. This review examines how DNA methylation, non-coding RNAs, and histone modifications drive excessive PI3K/AKT pathway activation. It also assesses the more limited evidence that PI3K/AKT signaling regulates these enzymes and reviews recent progress in combining PI3K inhibitors with epigenetic-targeting agents. We then consider the main barriers to clinical translation, including biomarker selection, treatment scheduling, and nanocarrier-based co-delivery. Clarifying this reciprocal regulation may support more rational, individualized therapeutic strategies for HCC.",
  "abstract_shown": true,
  "affiliations": [
    "The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology , , ,",
    "The First Affiliated Hospital of Zhengzhou University , , ,",
    "Yellow River Sanmenxia Hospital Affiliated to Henan University of Science and Technology , , ,"
  ],
  "article_type": "review article",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Zhibo Zhang"
    },
    {
      "affs": [
        1
      ],
      "name": "Jie Liu"
    },
    {
      "affs": [
        2
      ],
      "name": "Guofeng Lei"
    },
    {
      "affs": [
        0
      ],
      "name": "Xinjun Hu"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/fpqz0sywtnnpj.bib",
  "cited_by": 0,
  "doi": "10.3389/fcell.2026.1975140",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13727954/?tool=EBI",
  "id": "fpqz0sywtnnpj",
  "issns": [
    "2296-634X"
  ],
  "landing_url": "https://europepmc.org/article/PMC/PMC13727954",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Review"
    ],
    [
      "openalex",
      "1312|PI3K/AKT/mTOR signaling in cancer"
    ]
  ],
  "openalex": "W7223015854",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13727954/pdf/?tool=EBI",
  "pmcid": "PMC13727954",
  "pmid": "42978971",
  "published": "2026-10-20",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/fpqz0sywtnnpj.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T15:20:46Z",
      "native_id": "PMC:PMC13727954",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13727954"
    },
    {
      "first_seen": "2026-11-06T12:23:44Z",
      "native_id": "PMC13727954",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fcell.2026.1975140"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|PI3K/AKT/mTOR signaling in cancer",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Crosstalk between PI3K/AKT signaling and epigenetic regulation in hepatocellular carcinoma: molecular mechanisms and therapeutic opportunities",
  "title_text": "Crosstalk between PI3K/AKT signaling and epigenetic regulation in hepatocellular carcinoma: molecular mechanisms and therapeutic opportunities",
  "type": "peer-reviewed",
  "updated_at": "2026-11-07T12:21:03Z",
  "url": "https://research.draconitic.com/paper/fpqz0sywtnnpj",
  "venue": "Frontiers in cell and developmental biology",
  "versions": []
}