{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T23:43:04Z","timestamp":1789774984148,"version":"4.0.1"},"reference-count":219,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T00:00:00Z","timestamp":1765929600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"UPMC CHP Research Advisory Committee"},{"name":"UPMC CHP Foundation"},{"name":"an Independent Investigator Award from The RALLY Foundation","award":["22IN42"],"award-info":[{"award-number":["22IN42"]}]},{"DOI":"10.13039\/100001445","name":"Alex\u2019s Lemonade Stand Foundation","doi-asserted-by":"crossref","award":["1419786"],"award-info":[{"award-number":["1419786"]}],"id":[{"id":"10.13039\/100001445","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Hepatoblastoma (HB), the most common pediatric liver malignancy, tends to be highly curable although advanced or recurrent disease has less favorable outcomes. Because patients are invariably &lt;3\u20134 years of age, chemotherapies can cause significant long-term morbidities. Immortalized HB cell lines could be of great utility for drug screening, for the identification of novel therapeutic susceptibilities, and for studies requiring highly regulated and\/or rapidly changing in vitro environments. However, HB research is hampered by a paucity of these lines that could be used for such purposes, with only two human cell lines being readily available, neither of which represents the most common HB molecular subtypes. Recently, immortalized cell lines have been derived from murine HBs that are driven by the most common oncogenes and tumor suppressors associated with human tumors. These comprise five distinct groups associated with the deregulation of each of the four possible combinations of oncogenic forms of the \u03b2-catenin, YAP and NRF2 transcription factors or the over-expression of MYC. All five groups share many of the attributes and molecular signatures of actual human HBs. In addition, they have been used for purposes as diverse as identifying novel molecular targets through the use of Crispr-based screens and the demonstration that some HB cells can trans-differentiate into endothelial cells that facilitate tumor growth. The experience gained from these models and advances in the propagation of human hepatocytes in mice suggests that it may soon be possible to generate bespoke human immortalized human cell lines.<\/jats:p>","DOI":"10.3390\/cells14242013","type":"journal-article","created":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T13:42:52Z","timestamp":1765978972000},"page":"2013","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Hepatoblastoma Cell Lines: Past, Present and Future"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9666-8205","authenticated-orcid":false,"given":"Edward V.","family":"Prochownik","sequence":"first","affiliation":[{"name":"Division of Hematology\/Oncology, UPMC Children\u2019s Hospital, Pittsburgh, PA 15224, USA"},{"name":"Department of Microbiology and Molecular Genetics, School of Medicine, The University of Pittsburgh, Pittsburgh, PA 15213, USA"},{"name":"The Hillman Cancer Center, The University of Pittsburgh Medical Center, Pittsburgh, PA 15232, USA"},{"name":"The Pittsburgh Liver Research Center, The University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA"},{"name":"Rangos Research Center, Room 5124, 4401 Penn Avenue, Pittsburgh, PA 15224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8934-3104","authenticated-orcid":false,"given":"Colin M.","family":"Henchy","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, UPMC Children\u2019s Hospital, Pittsburgh, PA 15224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2551-3243","authenticated-orcid":false,"given":"Huabo","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, UPMC Children\u2019s Hospital, Pittsburgh, PA 15224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e29763","DOI":"10.1002\/pbc.29763","article-title":"Incidence and 5-year survival of children and adolescents with hepatoblastoma in the United States","volume":"69","author":"Kahla","year":"2022","journal-title":"Pediatr. 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