{
    "abstract": "Hepatoblastoma, the most common malignant liver tumor in pediatric patients, is characterized by a remarkably low mutation rate, thereby impeding targeted therapies. Current treatment regimens rely on conventional cytotoxic agents that often cause severe adverse effects, necessitating the search for novel, less toxic therapeutic approaches.\nIn this study, we explored the anti-tumor potential of heat shock protein 90 (HSP90) inhibitors using a unique collection of hepatoblastoma in vitro models.\nAmong the five tested inhibitors, we identified ganetespib as the most effective, significantly suppressing tumor cell growth while sparing healthy, non-tumor cells. Ganetespib treatment at low nanomolar concentrations markedly reduced cell proliferation, impaired long-term survival, and inhibited three-dimensional spheroid growth, ultimately leading to the induction of apoptosis. Mechanistically, ganetespib downregulated the expression of the HSP90 client protein cyclin-dependent kinase 1, a key cell cycle regulator controlling G2/M phase transition, which is heavily upregulated in hepatoblastoma. This disruption consequently resulted in cell cycle arrest, further contributing to its anti-tumor effects.\nHSP90 inhibition by ganetespib demonstrates significant potential as a novel therapeutic strategy for hepatoblastoma, offering a potential alternative to current cytotoxic treatments with fewer adverse effects.",
    "authors": [
        {
            "affiliation": "Department of Pediatric Surgery, Dr. von Hauner Children's Hospital, LMU University Hospital, 80337 Munich, Germany.",
            "firstname": "Lea Amelie",
            "initials": "LA",
            "lastname": "Jung"
        },
        {
            "affiliation": "Department of Pediatric Surgery, Dr. von Hauner Children's Hospital, LMU University Hospital, 80337 Munich, Germany.",
            "firstname": "Salih",
            "initials": "S",
            "lastname": "Demir"
        },
        {
            "affiliation": "Department of Pediatric Surgery, Dr. von Hauner Children's Hospital, LMU University Hospital, 80337 Munich, Germany.",
            "firstname": "Alina",
            "initials": "A",
            "lastname": "Hotes"
        },
        {
            "affiliation": "Natural Science Center for Basic Research and Development, Hiroshima University, Hiroshima 739-0046, Japan.",
            "firstname": "Eiso",
            "initials": "E",
            "lastname": "Hiyama"
        },
        {
            "affiliation": "Department of Pediatric Surgery, Graduate School of Medicine, Chiba University, Chiba 260-8677, Japan.",
            "firstname": "Tomoro",
            "initials": "T",
            "lastname": "Hishiki"
        },
        {
            "affiliation": "XenTech, 91000 Evry, France.",
            "firstname": "Emilie",
            "initials": "E",
            "lastname": "Indersie"
        },
        {
            "affiliation": "Bic\u00eatre Hospital, AP-HP Paris Saclay University, 94270 Paris, France.",
            "firstname": "Sophie",
            "initials": "S",
            "lastname": "Branchereau"
        },
        {
            "affiliation": "Champions Oncology, Inc., Rockville, MD 20850, USA.\nPediatric Research Institute (IRP), 35127 Padova, Italy.",
            "firstname": "Stefano",
            "initials": "S",
            "lastname": "Cairo"
        },
        {
            "affiliation": "Department of Pediatric Surgery, Dr. von Hauner Children's Hospital, LMU University Hospital, 80337 Munich, Germany.",
            "firstname": "Roland",
            "initials": "R",
            "lastname": "Kappler"
        }
    ],
    "conclusions": null,
    "copyrights": null,
    "doi": "10.3390/cancers17081341",
    "journal": "Cancers",
    "keywords": [
        "CDK1",
        "HSP90",
        "apoptosis",
        "ganetespib",
        "hepatoblastoma"
    ],
    "methods": null,
    "publication_date": "2025-04-26",
    "pubmed_id": "40282517",
    "results": "Among the five tested inhibitors, we identified ganetespib as the most effective, significantly suppressing tumor cell growth while sparing healthy, non-tumor cells. Ganetespib treatment at low nanomolar concentrations markedly reduced cell proliferation, impaired long-term survival, and inhibited three-dimensional spheroid growth, ultimately leading to the induction of apoptosis. Mechanistically, ganetespib downregulated the expression of the HSP90 client protein cyclin-dependent kinase 1, a key cell cycle regulator controlling G2/M phase transition, which is heavily upregulated in hepatoblastoma. This disruption consequently resulted in cell cycle arrest, further contributing to its anti-tumor effects.",
    "title": "Targeting HSP90 with Ganetespib to Induce CDK1 Degradation and Promote Cell Death in Hepatoblastoma.",
    "xml": "<Element 'PubmedArticle' at 0x788501cab650>"
}