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Although globally rare, it accounts for a large proportion of liver cancer in children and has poor survival rates in high-risk and metastatic cases. This review discusses the molecular mechanisms, diagnostic methods, and therapeutic strategies of HB. Mutations in the CTNNB1 gene and the activation of the Wnt\/\u03b2-catenin pathway are essential genetic factors. Furthermore, genetic syndromes like Beckwith\u2013Wiedemann syndrome (BWS) and Familial Adenomatous Polyposis (FAP) considerably heighten the risk of associated conditions. Additionally, epigenetic mechanisms, such as DNA methylation and the influence of non-coding RNAs (ncRNAs), are pivotal drivers of tumor development. Diagnostics include serum biomarkers, immunohistochemistry (IHC), and imaging techniques. Standard treatments are chemotherapy, surgical resection, and liver transplantation (LT). Emerging therapies like immunotherapy and targeted treatments offer hope against chemotherapy resistance. Future research will prioritize personalized medicine, novel biomarkers, and molecular-targeted therapies to improve survival outcomes.<\/jats:p>","DOI":"10.3390\/curroncol32030149","type":"journal-article","created":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T07:47:37Z","timestamp":1741074457000},"page":"149","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Hepatoblastoma: From Molecular Mechanisms to Therapeutic Strategies"],"prefix":"10.3390","volume":"32","author":[{"given":"Ling","family":"Fan","sequence":"first","affiliation":[{"name":"State Key Laboratory of Targeting Oncology, Guangxi Medical University, Nanning 530021, China"},{"name":"National Center for International Research of Bio-Targeting Theranostics, Guangxi Medical University, Nanning 530021, China"},{"name":"Guangxi Key Laboratory of Bio-Targeting Theranostics, Guangxi Medical University, Nanning 530021, China"},{"name":"Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Medical University, Nanning 530021, China"},{"name":"Guangxi Talent Highland of Major New Drugs Innovation and Development, Guangxi Medical University, Nanning 530021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jintong","family":"Na","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Targeting Oncology, Guangxi Medical University, Nanning 530021, China"},{"name":"National Center for International Research of Bio-Targeting Theranostics, Guangxi Medical University, Nanning 530021, China"},{"name":"Guangxi Key Laboratory of Bio-Targeting Theranostics, Guangxi Medical University, Nanning 530021, China"},{"name":"Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Medical University, Nanning 530021, China"},{"name":"Guangxi Talent Highland of Major New Drugs Innovation and Development, Guangxi Medical University, Nanning 530021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tieliu","family":"Shi","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Targeting Oncology, Guangxi Medical University, Nanning 530021, China"},{"name":"National Center for International Research of Bio-Targeting Theranostics, Guangxi Medical University, Nanning 530021, China"},{"name":"Guangxi Key Laboratory of Bio-Targeting Theranostics, Guangxi Medical University, Nanning 530021, China"},{"name":"Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Medical University, Nanning 530021, China"},{"name":"Guangxi Talent Highland of Major New Drugs Innovation and Development, Guangxi Medical University, Nanning 530021, China"},{"name":"Center for Bioinformatics and Computational Biology, Shanghai Key Laboratory of Regulatory Biology,  The Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China"},{"name":"Key Laboratory of Advanced Theory and Application in Statistics and Data Science (MOE), School of Statistics,  East China Normal University, Shanghai 200062, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Liao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Targeting Oncology, Guangxi Medical University, Nanning 530021, China"},{"name":"National Center for International Research of Bio-Targeting Theranostics, Guangxi Medical University, Nanning 530021, China"},{"name":"Guangxi Key Laboratory of Bio-Targeting Theranostics, Guangxi Medical University, Nanning 530021, China"},{"name":"Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Medical University, Nanning 530021, China"},{"name":"Guangxi Talent Highland of Major New Drugs Innovation and Development, Guangxi Medical University, Nanning 530021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"102765","DOI":"10.1016\/j.eclinm.2024.102765","article-title":"Worldwide burden of liver cancer across childhood and adolescence, 2000\u20132021: A systematic analysis of the Global Burden of Disease Study 2021","volume":"75","author":"Wu","year":"2024","journal-title":"EClinicalMedicine"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Zhu, L.R., Zheng, W., Gao, Q., Chen, T., Pan, Z.B., Cui, W., Cai, M., and Fang, H. 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