ArticleHepatology (Baltimore, Md.)2021
Olaparib Inhibits Tumor Growth of Hepatoblastoma in Patient-Derived Xenograft Models.
Article in Hepatology (Baltimore, Md.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 23 citations in OpenAlex.
- Pediatric Hepatoblastoma: From Developmental Molecular Mechanisms to Innovative Therapeutic Strategies.Cancers · 2026Review
- Review
- β-Catenin-Cohesin Ring-CEGRs/ALCDs Axis Activation Contributes to the Development of Hepatoblastoma and Fibrolamellar HCC.Molecular cancer research : MCR · 2025Article
- Patient-derived xenograft models: Current status, challenges, and innovations in cancer research.Genes & diseases · 2025Review
- From preneoplastic lesion to heterogenous tumor: recent insights into hepatoblastoma biology and therapeutic opportunities.Molecular cancer · 2025Review
- DNAJB1-PKAc Kinase Is Expressed in Young Patients with Pediatric Liver Cancers and Enhances Carcinogenic Pathways.Cancers · 2024Article
- Divergent WNT signaling and drug sensitivity profiles within hepatoblastoma tumors and organoids.Nature communications · 2024Article
- Article
- Cellular origin and molecular mechanisms of lung metastases in patients with aggressive hepatoblastoma.Hepatology communications · 2024Article
- SOCS2 inhibits hepatoblastoma metastasis via downregulation of the JAK2/STAT5 signal pathway.Scientific reports · 2023Article
- [Establishment of a patient-derived xenograft humanized mouse model for hepatoblastoma in children].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2023Article
- Article
- Current Approaches in Hepatoblastoma-New Biological Insights to Inform Therapy.Current oncology reports · 2022Review
- Establishment of childhood hepatoblastoma xenografts and evaluation of the anti-tumour effects of anlotinib, oxaliplatin and sorafenib.Pediatric surgery international · 2022Article
- Case report: Olaparib as an experimental therapy in a BRCA2-mutated patient with metastatic ovarian adenocarcinoma that originated from liver cancer.Frontiers in oncology · 2022Article
- Inducing Synergistic DNA Damage by TRIP13 and PARP1 Inhibitors Provides a Potential Treatment for Hepatocellular Carcinoma.Journal of Cancer · 2022Article
- Application of 3D Simulation Software in Chemotherapy and Hepatoblastoma Surgery in Children.Frontiers in surgery · 2022Article
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
BACKGROUND AND
aimsHepatoblastoma (HBL) is a devastating pediatric liver cancer with multiple treatment options, but it ultimately requires surgery for a cure. The most malicious form of HBL is a chemo-resistant aggressive tumor that is characterized by rapid growth, metastases, and poor response to treatment. Very little is known of the mechanisms of aggressive HBL, and recent focuses have been on developing alternative treatment strategies. In this study, we examined the role of human chromosomal regions, called aggressive liver cancer domains (ALCDs), in liver cancer and evaluated the mechanisms that activate ALCDs in aggressive HBL.
resultsWe found that ALCDs are critical regions of the human genome that are located on all human chromosomes, preferentially in intronic regions of the oncogenes and other cancer-associated genes. In aggressive HBL and in patients with Hepatocellular (HCC), JNK1/2 phosphorylates p53 at Ser6, which leads to the ph-S6-p53 interacting with and delivering the poly(adenosine diphosphate ribose) polymerase 1 (PARP1)/Ku70 complexes on the oncogenes containing ALCDs. The ph-S6-p53-PARP1 complexes open chromatin around ALCDs and activate multiple oncogenic pathways. We found that the inhibition of PARP1 in patient-derived xenografts (PDXs) from aggressive HBL by the Food and Drug Administration (FDA)-approved inhibitor olaparib (Ola) significantly inhibits tumor growth. Additionally, this is associated with the reduction of the ph-S6-p53/PARP1 complexes and subsequent inhibition of ALCD-dependent oncogenes. Studies in cultured cancer cells confirmed that the Ola-mediated inhibition of the ph-S6-p53-PARP1-ALCD axis inhibits proliferation of cancer cells.
conclusionsIn this study, we showed that aggressive HBL is moderated by ALCDs, which are activated by the ph-S6-p53/PARP1 pathway. By using the PARP1 inhibitor Ola, we suppressed tumor growth in HBL-PDX models, which demonstrated its utility in future clinical models.
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