RARE DISEASE
Hepatoblastoma
Hepatoblastoma
Hepatoblastoma
Drug discovery
7
drugs
With orphan designations
Overview
Hepatoblastoma is the most common pediatric liver malignancy, predominantly affecting children under age 3, with strong associations with prematurity and very low birth weight [1][6]. Treatment combines surgical resection with cisplatin-based chemotherapy, achieving >90% survival in localized disease but <80% in metastatic cases [4][7]. Staging follows the PRETEXT/POSTTEXT system to guide resectability [6], while emerging therapies like HDAC inhibitors show promise for high-risk cases [8].
Categories: rare hepatic diseases, rare neoplastic diseases, rare transplant-related disorders
Research Papers
1,579 drug discovery papers related to Hepatoblastoma, with 4 first-in-class and 5 next-in-class early-stage therapies forecasted to outperform the average preclinical success rate. Recent publications:
1,579 drug discovery papers related to Hepatoblastoma, with 4 first-in-class and 5 next-in-class early-stage therapies forecasted to outperform the average preclinical success rate. Recent publications:
2026-07-07 | Total vascular exclusion in pediatric hepatectomy: reducing hemorrhage without added morbidity.
Major hepatectomy in children carries distinct risks and challenges, with intraoperative hemorrhage being a critical determinant of morbidity and survival. Total vascular exclusion (TVE) provides complete vascular control, but its use in adults is associated with high morbidity. Evidence for pediatric hepatectomy is lacking. A single-center study of all children (<18 years) undergoing major hepatectomy between 2013 and 2023 was performed. Patients were grouped by TVE use. Primary outcomes were major complications (Clavien-Madadi ≥ III) and posthepatectomy liver dysfunction. Secondary outcomes included CCI, blood loss, transfusion, renal function, hospital stay, and oncologic outcomes. A total of 125 patients were included (68% with hepatoblastoma). TVE was applied in 67 children (53.6%) with a median duration of 18 min. No episodes of hemodynamic instability occurred during TVE. Outcomes including major complications (6.0% TVE vs. 6.9% non-TVE, p = 1.000), as well as intraoperative blood loss and transfusion, did not differ significantly between the groups. No patient developed clinically relevant posthepatectomy liver failure or renal dysfunction. This is the largest series of children undergoing hepatectomy using TVE. In contrast to adult liver surgery, where adverse physiological effects constrain its use, TVE can be safely performed in children, without increasing perioperative morbidity.
2026-07-02 | Integrative transcriptomic and CRISPR dependency analysis identifies hepatoblastoma-specific essential genes and actionable vulnerabilities.
Hepatoblastoma (HB) is the most common primary liver malignancy in childhood, yet its molecular determinants, functional dependencies, and therapeutic vulnerabilities remain incompletely characterized. Integrative analyses combining transcriptomic profiling with functional genomic datasets provide a strategy to identify essential genes, biomarkers predictive of tumor behavior and treatment response. Differential expression analysis comparing HB tumors with normal liver was processed on training cohort. These genes were integrated with DepMap CRISPR-Cas9 dependency scores to prioritize HB-essential candidates. Elastic Net regression was used to derive a 16-gene predictive signature, which was validated in an external cohort. Single-cell RNA-seq datasets were analyzed to assess expression patterns across hepatic and tumor-associated cell populations. A supervised deep-learning classifier was trained on single-cell profiles to distinguish tumor cells from hepatocytes, and SHAP values were computed to interpret gene contributions. Drug-gene interactions were queried using curated repressive compounds from DGIdb, and approved drugs were screened for relevance in pediatric cancer clinical trials. A total of 789 genes were found overexpressed in HB tumors from the training transcriptome cohort. Chronos DepMap analysis identified 73 HB-essential genes that were not essential in adult liver cancer cell lines (hepatocellular carcinoma and cholangiocarcinoma). Elastic-net tuning based on the expression of 16 HB-essential genes in the split training cohort enabled robust tumor-normal discrimination, with AUC = 0.88, specificity = 0.90, and sensitivity = 0.90 in internal validation. This performance was confirmed in an independent external cohort, achieving AUC = 0.99, specificity = 1.00, and sensitivity = 0.98. Single-cell validation further demonstrated tumor-specific enrichment of the signature. The deep-learning classifier (tumor cells vs. normal hepatocytes) reached high accuracy (AUC = 0.99; F1-score = 0.97), with SHAP analysis highlighting PEG10, GREB1, PLCB4, RHOBTB1, CRIM1, FSD1L, CORO2A, KIT, ANKRD50, HDAC11, ZNF233, SEMA7A, and FABP4 as major contributors. Six of these genes were confirmed to be absent or lowly expressed in the background liver microenvironment. Drug-gene interaction analysis identified HDAC11 as a potential therapeutic target of approved drugs used in pediatric oncology. This integrative framework combining transcriptomics, CRISPR dependency mapping, machine learning, and pharmacogenomic annotation identifies clinically relevant HB-essential genes and predictive molecular signatures for tumor identity. The derived expression-based scores provide tools for patient stratification, while drug-gene mapping highlights actionable vulnerabilities on HDAC11 with pediatric approved drugs that support rational drug repurposing strategies in hepatoblastoma.
2026-06-30 | Effective Use of Transarterial Chemoembolization (TACE) in an 8-Month-Old Infant with Hepatoblastoma PRETEXT III: A Case Study
Introduction: Hepatoblastoma (HB) is a rare primary malignant tumor of the liver in children. Treatment procedures for HB usually involve surgery and even liver transplantation, in addition to neoadjuvant or palliative systemic chemotherapy. However, the recent development of transarterial chemoembolization (TACE) procedures has provided an additional option that is considered quite effective in treating HB. This treatment procedure is believed to have many advantages as a treatment option prior to surgery and/or liver transplantation. This case is interesting to discuss because this procedure is still rarely performed in Indonesia. Whereas in many countries it has shown success and is quite desirable option both as a bridge therapy before surgery and palliative therapy. Case Presentation: We present a case of an 8-month-old baby boy diagnosed with HB. The patient had a history of preterm birth. Hemoglobin (Hb) level was 7 g/dL, and platelet count was elevated. Alpha-fetoprotein (AFP) levels were elevated to 122,010 ng/dL. Ultrasonography showed a large solid mass in the right liver lobe, raising suspicion of malignancy. Contrast enhanced 3-phase computed tomography (CT) scan imaging showed a solid mass in the right lobe of the liver that was contrast-enhanced, hypovascularized, contained intra-tumor necrotic components, had ill-defined borders, and was not encapsulated. It measured approximately 9.02 x 9.94 x 9.93 cm, and appeared to cover almost the entire right lobe of the liver. This finding was diagnosed as PRETEXT III hepatoblastoma. An experienced interventional radiologist performed TACE with cisplatin agent. Subsequent evaluation 20 days after the first TACE, the size of the tumor mass had reduced by 20% from the previous size. This finding warrants consideration of the next optimal therapeutic approach, i.e., whether to proceed with surgical intervention or perform subsequent TACE prior to surgery. In our case, we proceeded with a repeat of TACE followed by surgery.Conclusions: Transarterial chemoembolization appears to be one of the effective treatment options for large and invasive HB, as experience has shown that TACE can shrink tumor size, provide clearer borders, and reduce alpha-fetoprotein (AFP) levels after the first TACE. TACE can thus facilitate more optimal surgical and transplantation procedures. Thus, we believe that TACE has the potential to become a recognized HB treatment option in the future.
2026-07-07 | Total vascular exclusion in pediatric hepatectomy: reducing hemorrhage without added morbidity.
Major hepatectomy in children carries distinct risks and challenges, with intraoperative hemorrhage being a critical determinant of morbidity and survival. Total vascular exclusion (TVE) provides complete vascular control, but its use in adults is associated with high morbidity. Evidence for pediatric hepatectomy is lacking. A single-center study of all children (<18 years) undergoing major hepatectomy between 2013 and 2023 was performed. Patients were grouped by TVE use. Primary outcomes were major complications (Clavien-Madadi ≥ III) and posthepatectomy liver dysfunction. Secondary outcomes included CCI, blood loss, transfusion, renal function, hospital stay, and oncologic outcomes. A total of 125 patients were included (68% with hepatoblastoma). TVE was applied in 67 children (53.6%) with a median duration of 18 min. No episodes of hemodynamic instability occurred during TVE. Outcomes including major complications (6.0% TVE vs. 6.9% non-TVE, p = 1.000), as well as intraoperative blood loss and transfusion, did not differ significantly between the groups. No patient developed clinically relevant posthepatectomy liver failure or renal dysfunction. This is the largest series of children undergoing hepatectomy using TVE. In contrast to adult liver surgery, where adverse physiological effects constrain its use, TVE can be safely performed in children, without increasing perioperative morbidity.
2026-07-02 | Integrative transcriptomic and CRISPR dependency analysis identifies hepatoblastoma-specific essential genes and actionable vulnerabilities.
Hepatoblastoma (HB) is the most common primary liver malignancy in childhood, yet its molecular determinants, functional dependencies, and therapeutic vulnerabilities remain incompletely characterized. Integrative analyses combining transcriptomic profiling with functional genomic datasets provide a strategy to identify essential genes, biomarkers predictive of tumor behavior and treatment response. Differential expression analysis comparing HB tumors with normal liver was processed on training cohort. These genes were integrated with DepMap CRISPR-Cas9 dependency scores to prioritize HB-essential candidates. Elastic Net regression was used to derive a 16-gene predictive signature, which was validated in an external cohort. Single-cell RNA-seq datasets were analyzed to assess expression patterns across hepatic and tumor-associated cell populations. A supervised deep-learning classifier was trained on single-cell profiles to distinguish tumor cells from hepatocytes, and SHAP values were computed to interpret gene contributions. Drug-gene interactions were queried using curated repressive compounds from DGIdb, and approved drugs were screened for relevance in pediatric cancer clinical trials. A total of 789 genes were found overexpressed in HB tumors from the training transcriptome cohort. Chronos DepMap analysis identified 73 HB-essential genes that were not essential in adult liver cancer cell lines (hepatocellular carcinoma and cholangiocarcinoma). Elastic-net tuning based on the expression of 16 HB-essential genes in the split training cohort enabled robust tumor-normal discrimination, with AUC = 0.88, specificity = 0.90, and sensitivity = 0.90 in internal validation. This performance was confirmed in an independent external cohort, achieving AUC = 0.99, specificity = 1.00, and sensitivity = 0.98. Single-cell validation further demonstrated tumor-specific enrichment of the signature. The deep-learning classifier (tumor cells vs. normal hepatocytes) reached high accuracy (AUC = 0.99; F1-score = 0.97), with SHAP analysis highlighting PEG10, GREB1, PLCB4, RHOBTB1, CRIM1, FSD1L, CORO2A, KIT, ANKRD50, HDAC11, ZNF233, SEMA7A, and FABP4 as major contributors. Six of these genes were confirmed to be absent or lowly expressed in the background liver microenvironment. Drug-gene interaction analysis identified HDAC11 as a potential therapeutic target of approved drugs used in pediatric oncology. This integrative framework combining transcriptomics, CRISPR dependency mapping, machine learning, and pharmacogenomic annotation identifies clinically relevant HB-essential genes and predictive molecular signatures for tumor identity. The derived expression-based scores provide tools for patient stratification, while drug-gene mapping highlights actionable vulnerabilities on HDAC11 with pediatric approved drugs that support rational drug repurposing strategies in hepatoblastoma.
2026-06-30 | Effective Use of Transarterial Chemoembolization (TACE) in an 8-Month-Old Infant with Hepatoblastoma PRETEXT III: A Case Study
Introduction: Hepatoblastoma (HB) is a rare primary malignant tumor of the liver in children. Treatment procedures for HB usually involve surgery and even liver transplantation, in addition to neoadjuvant or palliative systemic chemotherapy. However, the recent development of transarterial chemoembolization (TACE) procedures has provided an additional option that is considered quite effective in treating HB. This treatment procedure is believed to have many advantages as a treatment option prior to surgery and/or liver transplantation. This case is interesting to discuss because this procedure is still rarely performed in Indonesia. Whereas in many countries it has shown success and is quite desirable option both as a bridge therapy before surgery and palliative therapy. Case Presentation: We present a case of an 8-month-old baby boy diagnosed with HB. The patient had a history of preterm birth. Hemoglobin (Hb) level was 7 g/dL, and platelet count was elevated. Alpha-fetoprotein (AFP) levels were elevated to 122,010 ng/dL. Ultrasonography showed a large solid mass in the right liver lobe, raising suspicion of malignancy. Contrast enhanced 3-phase computed tomography (CT) scan imaging showed a solid mass in the right lobe of the liver that was contrast-enhanced, hypovascularized, contained intra-tumor necrotic components, had ill-defined borders, and was not encapsulated. It measured approximately 9.02 x 9.94 x 9.93 cm, and appeared to cover almost the entire right lobe of the liver. This finding was diagnosed as PRETEXT III hepatoblastoma. An experienced interventional radiologist performed TACE with cisplatin agent. Subsequent evaluation 20 days after the first TACE, the size of the tumor mass had reduced by 20% from the previous size. This finding warrants consideration of the next optimal therapeutic approach, i.e., whether to proceed with surgical intervention or perform subsequent TACE prior to surgery. In our case, we proceeded with a repeat of TACE followed by surgery.Conclusions: Transarterial chemoembolization appears to be one of the effective treatment options for large and invasive HB, as experience has shown that TACE can shrink tumor size, provide clearer borders, and reduce alpha-fetoprotein (AFP) levels after the first TACE. TACE can thus facilitate more optimal surgical and transplantation procedures. Thus, we believe that TACE has the potential to become a recognized HB treatment option in the future.
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Drug Discovery Landscape
7 orphan drug designations for Hepatoblastoma.
7 orphan drug designations for Hepatoblastoma.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
genetically engineered, replication-competent vesicular stomatitis virus (VSV)-based oncolytic viral therapy | other | FDA | 2026-05-27 | — | Humane Genomics Inc. |
N-hydroxy-N-(methylacylfulvene)urea | small molecules | FDA | 2024-10-28 | — | Lantern Pharma Inc. |
an autologous T-cell immunotherapy (ET140203) | cell therapies | FDA | 2022-10-07 | — | Eureka Therapeutics, Inc. |
[11C]Acetic Acid | small molecules | FDA | 2019-02-28 | — | Advanced Imaging Projects, LLC |
Doxorubicin | small molecules | EMA | 2015-07-28 | — | Double Bond Pharmaceutical AB |
Iodine I 123 murine monoclonal antibody to alpha-fetoprotein | antibodies | FDA | 1988-09-30 | — | Immunomedics, Inc. |
Iodine I 131 murine monoclonal antibody to alpha-fetoprotein | antibodies | FDA | 1988-09-30 | — | Immunomedics, Inc. |
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