ArticleMolecular cancer therapeutics2023
Identification of IGF2 as Genomic Driver and Actionable Therapeutic Target in Hepatoblastoma.
Article in Molecular cancer therapeutics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 14 citations in OpenAlex.
- Bibliometric and clinical trial landscape of hepatoblastoma (2000-2024): a multi-database analysis of global research.Frontiers in oncology · 2026Pooled it
- Article
- HBx-Associated Reactivation of the IGF2 Locus in Chronic HBV Infection and HBV-Related Hepatocarcinogenesis: Evidence Boundaries and Biomarker Implications.Biomedicines · 2026Review
- Effective therapeutic targeting of CTNNB1-mutant hepatoblastoma with WNTinib.Molecular oncology · 2026Article
- ALKBH1 gene polymorphisms confer hepatoblastoma susceptibility in Chinese children.Scientific reports · 2026Article
- Targeting MED23 inhibits hepatocellular carcinoma development by suppressing compensatory proliferation and facilitating ROS-mediated cell death.Cell death & disease · 2025Article
- Organoid models in oncology: advancing precision cancer therapy and vaccine development.Cancer biology & medicine · 2025Review
- Malignant Hepatoblast-Like Cells Sustain Stemness via IGF2-Dependent Cholesterol Accumulation in Hepatoblastoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Hepatoblastoma: From Molecular Mechanisms to Therapeutic Strategies.Current oncology (Toronto, Ont.) · 2025Review
- Neutrophil-induced pyroptosis promotes survival in patients with hepatoblastoma.Cancer immunology, immunotherapy : CII · 2025Article
- Metabolic and Epigenetic Mechanisms in Hepatoblastoma: Insights into Tumor Biology and Therapeutic Targets.Genes · 2024Review
- A novel imprinted locus on bovine chromosome 18 homologous with human chromosome 16q24.1.Molecular genetics and genomics : MGG · 2024Article
- Summary of biological research on hepatoblastoma: a scoping review.Frontiers in pediatrics · 2024Article
- Article
- Effects of methylation and imprinting expression of Insulin-like growth factor 2 gene in gastric cancer.Cancer biomarkers : section A of Disease markers · 2023Article
Corrections and comments
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Authors and funding
29 authors at 12 institutions in 7 countries.
Funding
Abstract
Management of hepatoblastoma (HB), the most frequent pediatric liver cancer, is based on surgical resection and perioperative chemotherapy regimens. In this study, we aimed to identify actionable targets in HB and assess the efficacy of molecular therapies in preclinical models of HB. Paired tumor and adjacent tissues from 31 HBs and a validation set of 50 HBs were analyzed using RNA-seq, SNP, and methylation arrays. IGF2 overexpression was identified as the top targetable HB driver, present in 71% of HBs (22/31). IGF2high tumors displayed progenitor cell features and shorter recurrence-free survival. IGF2 overexpression was associated in 91% of cases with fetal promoter hypomethylation, ICR1 deregulation, 11p15.5 loss of heterozygosity or miR483-5p overexpression. The antitumor effect of xentuzumab (a monoclonal antibody targeting IGF1/2) alone or in combination with the conventional therapeutic agent cisplatin was assessed in HB cell lines, in PDX-derived HB organoids and in a xenograft HB murine model. The combination of xentuzumab with cisplatin showed strong synergistic antitumor effects in organoids and in IGF2high cell lines. In mice (n = 55), the combination induced a significant decrease in tumor volume and improved survival compared with cisplatin alone. These results suggest that IGF2 is an HB actionable driver and that, in preclinical models of HB, the combination of IGF1/2 inhibition with cisplatin induces superior antitumor effects than cisplatin monotherapy. Overall, our study provides a rationale for testing IGF2 inhibitors in combination with cisplatin in HB patients with IGF2 overexpression.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.