{"doi":"10.1002/1878-0261.70168","title":"Effective therapeutic targeting of <i>CTNNB1</i> ‐mutant hepatoblastoma with <scp>WNTinib</scp>","abstract":"Hepatoblastoma (HB), the most frequent pediatric liver cancer (2.16 cases/million), has surgery and perioperative chemotherapy as primary treatment, with severe lifelong side effects. This study evaluates the efficacy of the Wnt/ CTNNB1 inhibitor WNTinib as a potential HB treatment, since CTNNB1 mutations occur in 70–90% of HBs. WNTinib's efficacy was assessed in three animal models ( n = 48): (a) patient‐derived xenograft (PDX) HB tumors ( n = 5 CTNNB1‐ mutant, n = 1 CTNNB1 wild‐type) implanted in NSG mice; (b) PDX‐derived TT001‐ and (c) HepG2‐HB cells subcutaneously implanted in Fox1 nu mice; and in two patient‐derived organoids from CTNNB1 ‐mutant HBs. WNTinib delayed tumor growth in n = 4/5 CTNNB1 ‐mutant PDX models and significantly improved survival versus controls ( P = 0.03), with no effect in the wild‐type model. Further, in the TT001 and HepG2 models, WNTinib reduced tumor growth ( P &lt; 0.05 and P = 0.002) and extended survival ( P = 0.03 and P = 0.008), respectively. In HB organoids, WNTinib demonstrated greater efficacy than standard‐of‐care cisplatin ( P = 0.009, org‐1), and its antitumor effect was further enhanced when combined with chemotherapy ( P = 0.01, org‐1; P = 0.007, org‐22). WNTinib delays tumor progression and increases survival in CTNNB1 ‐mutated HB models, providing rationale to explore its use in human HB.","journal":"Molecular Oncology","year":2025,"id":584560,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.957,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1208292,"name":"Júlia Huguet‐Pradell","orcid":"0000-0003-1489-356X","position":1,"is_corresponding":false},{"id":279339,"name":"Jordi Abril‐Fornaguera","orcid":"0000-0002-5871-4052","position":2,"is_corresponding":false},{"id":463789,"name":"Albert Gris‐Oliver","orcid":"0000-0003-1802-9541","position":3,"is_corresponding":false},{"id":1490670,"name":"Alex Rialdi","orcid":null,"position":4,"is_corresponding":false},{"id":763127,"name":"Elisa Fernández‐Martínez","orcid":"0009-0008-4390-5615","position":5,"is_corresponding":false},{"id":621644,"name":"Carla Montironi","orcid":"0000-0002-1453-2193","position":6,"is_corresponding":false},{"id":710651,"name":"Vanessa Del Pozo","orcid":null,"position":7,"is_corresponding":false},{"id":423424,"name":"Peter Houghton","orcid":null,"position":8,"is_corresponding":false},{"id":1027628,"name":"Laura Zanatto","orcid":null,"position":9,"is_corresponding":false},{"id":626328,"name":"Agavni Mesropian","orcid":"0000-0002-0604-4755","position":10,"is_corresponding":false},{"id":1284212,"name":"Ieva Keraite","orcid":"0000-0003-1974-9479","position":11,"is_corresponding":false},{"id":231500,"name":"Swan N. Thung","orcid":"0000-0003-4407-2295","position":12,"is_corresponding":false},{"id":1034386,"name":"Carolina Armengol","orcid":"0000-0002-4690-4027","position":13,"is_corresponding":false},{"id":596046,"name":"Pau Sancho‐Bru","orcid":"0000-0001-5569-9259","position":14,"is_corresponding":false},{"id":23521,"name":"Ernesto Guccione","orcid":"0000-0001-7764-5307","position":15,"is_corresponding":false},{"id":279340,"name":"Roser Pinyol","orcid":"0000-0002-0288-6314","position":16,"is_corresponding":false},{"id":228879,"name":"Josep M. Llovet","orcid":"0000-0003-0547-2667","position":17,"is_corresponding":false},{"id":626329,"name":"Ugne Balaseviciute","orcid":"0000-0002-4256-4336","position":0,"is_corresponding":true}],"reference_count":33,"raw_metadata":null,"created_at":"2026-07-19T02:59:16.166424Z","pmid":"41359441","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}