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While the prognosis is favorable when the tumor can be resected, the outcome is dismal for patients with progressed HB. Therefore, a better understanding of the molecular mechanisms responsible for HB is imperative for early detection and effective treatment. Sequencing analysis of human HB specimens unraveled the pivotal role of Wnt\/\u03b2-catenin pathway activation in this disease. Nonetheless, \u03b2-catenin activation alone does not suffice to induce HB, implying the need for additional alterations. Perturbations of several pathways, including Hippo, Hedgehog, NRF2\/KEAP1, HGF\/c-Met, NK-1R\/SP, and PI3K\/AKT\/mTOR cascades and aberrant activation of c-MYC, n-MYC, and EZH2 proto-oncogenes, have been identified in HB, although their role requires additional investigation. Here, we summarize the current knowledge on HB molecular pathogenesis, the relevance of the preclinical findings for the human disease, and the innovative therapeutic strategies that could be beneficial for the treatment of HB patients.<\/jats:p>","DOI":"10.1055\/s-0040-1722645","type":"journal-article","created":{"date-parts":[[2021,1,20]],"date-time":"2021-01-20T23:51:46Z","timestamp":1611186706000},"page":"028-041","source":"Crossref","is-referenced-by-count":57,"title":["Molecular Mechanisms of Hepatoblastoma"],"prefix":"10.1055","volume":"41","author":[{"given":"Yi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, China"},{"name":"Department of Bioengineering and Therapeutic Sciences and Liver Center, University of California, San Francisco, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Solinas","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Sassari, Sassari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Cairo","sequence":"additional","affiliation":[{"name":"XenTech, Evry, France"},{"name":"Istituto di Ricerca Pediatrica, Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Evert","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University of Regensburg, Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Bioengineering and Therapeutic Sciences and Liver Center, University of California, San Francisco, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego 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