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
1,595 drug discovery papers about Hepatoblastoma, with 4 first-in-class and 5 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
1,595 drug discovery papers about Hepatoblastoma, with 4 first-in-class and 5 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-08-14 | Antimicrobial, anti-biofilm, and anticancer activities of green-synthesized silver nanoparticles using Crossostephium chinense (L.) Makino aqueous leaf extract.
The increasing burden of infectious diseases, driven by microbial pathogenicity and antimicrobial resistance, necessitates the development of effective and sustainable antimicrobial strategies. In that context, this study reports, for the first time, the green synthesis of silver nanoparticles (AgNPs) using an aqueous extract of Crossostephium chinense (L.) Makino (CC) leaves, wherein plant-derived phytochemicals act as natural reducing and capping agents. Mass spectrometric analyses of CC aqueous leaf extract identified 62 possible metabolites, including flavonoids, phenolics, and terpenoids, that possibly facilitate nanoparticle synthesis. The synthesized C. chinense-derived silver nanoparticles (CC-AgNPs) were characterized as moderately stable, crystalline, spherical with sizes ranging from 20-80 nm. CC-AgNPs displayed broad-spectrum antimicrobial activity, showing the greatest susceptibility in Bacillus subtilis and Pseudomonas aeruginosa, with a minimum inhibitory concentration (MIC) of 6 μg/mL, while electron microscopy confirmed severe structural damage to bacterial membranes. Furthermore, CC-AgNPs displayed strong antibiofilm activity, achieving up to 92% biofilm inhibition in B. subtilis at 12 μg/mL. The anticancer potential of CC-AgNPs was evaluated against breast cancer (MCF-7 and MDA-MB-231), chronic myelogenous leukemia (K562), and hepatoblastoma (HepG2) cell lines. Among these, MDA-MB-231 cells were the most sensitive, exhibiting the lowest IC50 value. Further mechanistic investigations in MDA-MB-231 cells demonstrated apoptosis induction, as evidenced by nuclear fragmentation, Annexin V/PI staining and activation of caspases. In conclusion, these findings highlight CC-AgNPs as promising candidates for antimicrobial, antibiofilm, and anticancer applications.
2026-08-13 | [Efficacy comparisons of chemotherapy regimens with different intensities in high-risk pediatric hepatoblastoma].
Objective: To evaluate the efficacy of different chemotherapy regimens in children with high-risk hepatoblastoma (HB). Methods: A retrospective cohort study was conducted on 99 patients under 18 years old with high-risk HB treated at Sun Yat-sen University Cancer Center between December 2004 and July 2024. The patients were divided into three groups: the PLADO regimen (cisplatin in combination with doxorubicin, n=27), the C5VD/IIV regimen (alternating cycles of cisplatin/5-flourouracil/vincristine/doxorubicin with irinotecan/ifosfamide/vincristine, n=29), and the modified SIOPEL-4 regimen (the original SIOPEL-4 regimen with omitted high-dose cisplatin on day15, n=43). Short-term efficacy, adverse effects, and long-term survival were compared among the three groups. Results: The objective response rates for the PLADO, C5VD/IIV, and modified SIOPEL-4 groups were 73.9% (17/23), 70.8% (17/24), and 88.6% (31/35), respectively, with no statistically significant difference among the three groups (P=0.190). The disease control rates were 82.6% (19/23), 83.3% (20/24), and 100.0% (35/35), the 3-year progression-free survival (PFS) rates were 19.2%, 37.0%, and 56.7%, and the 3-year overall survival (OS) rates were 69.2%, 55.6%, and 79.0%, respectively. The modified SIOPEL-4 group showed significantly better disease control rate and PFS rate compared withthe other two groups (both P＜0.05). After merging the PLADO and C5VD/IIV groups, the modified SIOPEL-4 group demonstrated significantly superior PFS and OS rates (both P＜0.05). Conclusions: The efficacy of modified SIOPEL-4 regimen in treating high-risk HB is superior compared with those of PLADO and C5VD/IIV regimens, but there remains room for further improvement in efficacy. Intensifying supportive care and pursuing aggressive local therapies, especially upfront liver transplantation for locally inoperable tumors, may further improve outcomes.
2026-08-12 | Integrated Lineage Tracing in Hepatoblastoma Finds a Plasticity-Proliferation Axis That Drives Post-Treatment Adaptation
Hepatoblastoma (HB) has one of the lowest mutational burdens among childhood cancers, limiting the role of genetic selection. Nevertheless ~20% of patients relapse, implicating non-genetic mechanisms, such as phenotypic plasticity, in treatment adaptation. The temporal and clonal dynamics of post-treatment plasticity in HB remain poorly defined. Here, we integrate expressed DNA barcoding approaches with single-cell multiomics in preclinical models to simultaneously trace clonal and phenotypic dynamics following cisplatin treatment.We observe that cisplatin selects for progenitor-like states, which persist as reservoirs for phenotypic re-diversification. Barcode lineage tracing reveals a subset of persister clones stochastically resume proliferation and transition from less- to more-differentiated phenotypes, an observation also captured in patient data. Pseudotime and landscape approaches identify a plasticity-proliferation axis underlying recovery post-treatment, driven by coordinated activation of E2F transcription factors and their downstream target BIRC5 (survivin). Downregulation and pharmacological inhibition of BIRC5 disrupt this axis, shifting phenotypic dynamics towards less-differentiated states and killing cisplatin-persister cells, supporting a role for BIRC5 in plasticity-led awakening from persistence. Consistently, elevated BIRC5 expression is associated with poor patient outcome.Together, these findings establish a mechanistic link between persistence, phenotypic plasticity, and stochastic clonal outgrowth in HB, and identify BIRC5 as a regulator of plasticity-driven adaptation and a therapeutically actionable vulnerability to halt treatment adaptation.
2026-08-10 | DUSP9 Regulates Hepatoblastoma Progression With Implications for Diagnosis and Targeted Therapy.
This study investigated the mechanistic role of DUSP9 in hepatoblastoma (HB) development and progression to provide new insights into the diagnosis and treatment of pediatric HB. Pediatric HB mRNA expression data were obtained from the GEO database. Differentially expressed genes (DEGs) between patients with metastatic and non-metastatic HB were analyzed using the R software, followed by a functional annotation of the DEGs. Least Absolute Shrinkage and Selection Operator regression and Support Vector Machine-Recursive Feature Elimination machine learning methods were employed to further screen for DEGs and identify DUSP9 as a key feature gene. The diagnostic efficacy of DUSP9 was evaluated using the area under the receiver operating characteristic curve. Additionally, in vitro and in vivo functional experiments were conducted to determine the effects of DUSP9 on HB progression. A total of 33 DEGs were identified. Gene Ontology analysis revealed that these DEGs were mainly associated with xenobiotics and fatty acid metabolism. Kyoto Encyclopedia of Genes and Genomes analysis indicated involvement in regulating active transmembrane transporter activity and cytochrome P450-mediated xenobiotic metabolism. Machine learning methods identified DUSP9 as a pivotal feature gene that was significantly upregulated in HB tumor tissues. In vitro functional assays demonstrated that DUSP9 knockdown markedly inhibited the proliferation and migration of HB cells. Additionally, western blot analysis revealed increased expression of epithelial markers and decreased expression of mesenchymal markers, along with a significant reduction in the phosphorylation of markers related to the MAPK signaling pathway. DUSP9 plays a crucial role in HB cell proliferation, migration, and epithelial-mesenchymal transition (EMT), potentially promoting tumor progression by regulating the MAPK signaling pathway.
2026-07-29 | SMAP1 promotes hepatoblastoma cell proliferation by modulating the C-Kit-activated ERK/MAPK pathway.
Hepatoblastoma (HB) is the most common pediatric liver malignancy. We investigated the role of SMAP1 in HB proliferation and its mechanism. Sixty-seven HB tissues were analyzed for SMAP1 expression via immunohistochemistry and correlated with clinical outcomes. qRT-PCR quantified SMAP1 mRNA in HB cell lines versus normal hepatocytes. SMAP1 was knocked down (siRNA/lentivirus) or overexpressed (plasmid) in HB cells; proliferation was assessed by CCK-8 and colony formation. A nude-mouse xenograft model was used to evaluate tumorigenicity. Western blotting determined C-Kit and ERK/MAPK pathway activity after SMAP1 modulation. Rescue experiments used ERK activator C16-PAF, inhibitor U0126, or C-Kit inhibitor ISCK03. SMAP1 was upregulated in HB and predicted poor prognosis. Knockdown reduced C-Kit, p-C-Kit, and p-ERK1/2, inhibited proliferation and colony formation, and suppressed xenograft growth. Overexpression produced opposite effects. U0126 reversed ERK1/2 phosphorylation and p-Rb in SMAP1-overexpressing cells, whereas C16-PAF restored ERK signaling and c-Myc/p-Rb in knockdown cells. ISCK03 blocked C-Kit/ERK activation prompted by SMAP1 overexpression. SMAP1 drives HB progression by activating C-Kit-ERK/MAPK signaling, representing a potential therapeutic target.
2026-08-14 | Antimicrobial, anti-biofilm, and anticancer activities of green-synthesized silver nanoparticles using Crossostephium chinense (L.) Makino aqueous leaf extract.
The increasing burden of infectious diseases, driven by microbial pathogenicity and antimicrobial resistance, necessitates the development of effective and sustainable antimicrobial strategies. In that context, this study reports, for the first time, the green synthesis of silver nanoparticles (AgNPs) using an aqueous extract of Crossostephium chinense (L.) Makino (CC) leaves, wherein plant-derived phytochemicals act as natural reducing and capping agents. Mass spectrometric analyses of CC aqueous leaf extract identified 62 possible metabolites, including flavonoids, phenolics, and terpenoids, that possibly facilitate nanoparticle synthesis. The synthesized C. chinense-derived silver nanoparticles (CC-AgNPs) were characterized as moderately stable, crystalline, spherical with sizes ranging from 20-80 nm. CC-AgNPs displayed broad-spectrum antimicrobial activity, showing the greatest susceptibility in Bacillus subtilis and Pseudomonas aeruginosa, with a minimum inhibitory concentration (MIC) of 6 μg/mL, while electron microscopy confirmed severe structural damage to bacterial membranes. Furthermore, CC-AgNPs displayed strong antibiofilm activity, achieving up to 92% biofilm inhibition in B. subtilis at 12 μg/mL. The anticancer potential of CC-AgNPs was evaluated against breast cancer (MCF-7 and MDA-MB-231), chronic myelogenous leukemia (K562), and hepatoblastoma (HepG2) cell lines. Among these, MDA-MB-231 cells were the most sensitive, exhibiting the lowest IC50 value. Further mechanistic investigations in MDA-MB-231 cells demonstrated apoptosis induction, as evidenced by nuclear fragmentation, Annexin V/PI staining and activation of caspases. In conclusion, these findings highlight CC-AgNPs as promising candidates for antimicrobial, antibiofilm, and anticancer applications.
2026-08-13 | [Efficacy comparisons of chemotherapy regimens with different intensities in high-risk pediatric hepatoblastoma].
Objective: To evaluate the efficacy of different chemotherapy regimens in children with high-risk hepatoblastoma (HB). Methods: A retrospective cohort study was conducted on 99 patients under 18 years old with high-risk HB treated at Sun Yat-sen University Cancer Center between December 2004 and July 2024. The patients were divided into three groups: the PLADO regimen (cisplatin in combination with doxorubicin, n=27), the C5VD/IIV regimen (alternating cycles of cisplatin/5-flourouracil/vincristine/doxorubicin with irinotecan/ifosfamide/vincristine, n=29), and the modified SIOPEL-4 regimen (the original SIOPEL-4 regimen with omitted high-dose cisplatin on day15, n=43). Short-term efficacy, adverse effects, and long-term survival were compared among the three groups. Results: The objective response rates for the PLADO, C5VD/IIV, and modified SIOPEL-4 groups were 73.9% (17/23), 70.8% (17/24), and 88.6% (31/35), respectively, with no statistically significant difference among the three groups (P=0.190). The disease control rates were 82.6% (19/23), 83.3% (20/24), and 100.0% (35/35), the 3-year progression-free survival (PFS) rates were 19.2%, 37.0%, and 56.7%, and the 3-year overall survival (OS) rates were 69.2%, 55.6%, and 79.0%, respectively. The modified SIOPEL-4 group showed significantly better disease control rate and PFS rate compared withthe other two groups (both P＜0.05). After merging the PLADO and C5VD/IIV groups, the modified SIOPEL-4 group demonstrated significantly superior PFS and OS rates (both P＜0.05). Conclusions: The efficacy of modified SIOPEL-4 regimen in treating high-risk HB is superior compared with those of PLADO and C5VD/IIV regimens, but there remains room for further improvement in efficacy. Intensifying supportive care and pursuing aggressive local therapies, especially upfront liver transplantation for locally inoperable tumors, may further improve outcomes.
2026-08-12 | Integrated Lineage Tracing in Hepatoblastoma Finds a Plasticity-Proliferation Axis That Drives Post-Treatment Adaptation
Hepatoblastoma (HB) has one of the lowest mutational burdens among childhood cancers, limiting the role of genetic selection. Nevertheless ~20% of patients relapse, implicating non-genetic mechanisms, such as phenotypic plasticity, in treatment adaptation. The temporal and clonal dynamics of post-treatment plasticity in HB remain poorly defined. Here, we integrate expressed DNA barcoding approaches with single-cell multiomics in preclinical models to simultaneously trace clonal and phenotypic dynamics following cisplatin treatment.We observe that cisplatin selects for progenitor-like states, which persist as reservoirs for phenotypic re-diversification. Barcode lineage tracing reveals a subset of persister clones stochastically resume proliferation and transition from less- to more-differentiated phenotypes, an observation also captured in patient data. Pseudotime and landscape approaches identify a plasticity-proliferation axis underlying recovery post-treatment, driven by coordinated activation of E2F transcription factors and their downstream target BIRC5 (survivin). Downregulation and pharmacological inhibition of BIRC5 disrupt this axis, shifting phenotypic dynamics towards less-differentiated states and killing cisplatin-persister cells, supporting a role for BIRC5 in plasticity-led awakening from persistence. Consistently, elevated BIRC5 expression is associated with poor patient outcome.Together, these findings establish a mechanistic link between persistence, phenotypic plasticity, and stochastic clonal outgrowth in HB, and identify BIRC5 as a regulator of plasticity-driven adaptation and a therapeutically actionable vulnerability to halt treatment adaptation.
2026-08-10 | DUSP9 Regulates Hepatoblastoma Progression With Implications for Diagnosis and Targeted Therapy.
This study investigated the mechanistic role of DUSP9 in hepatoblastoma (HB) development and progression to provide new insights into the diagnosis and treatment of pediatric HB. Pediatric HB mRNA expression data were obtained from the GEO database. Differentially expressed genes (DEGs) between patients with metastatic and non-metastatic HB were analyzed using the R software, followed by a functional annotation of the DEGs. Least Absolute Shrinkage and Selection Operator regression and Support Vector Machine-Recursive Feature Elimination machine learning methods were employed to further screen for DEGs and identify DUSP9 as a key feature gene. The diagnostic efficacy of DUSP9 was evaluated using the area under the receiver operating characteristic curve. Additionally, in vitro and in vivo functional experiments were conducted to determine the effects of DUSP9 on HB progression. A total of 33 DEGs were identified. Gene Ontology analysis revealed that these DEGs were mainly associated with xenobiotics and fatty acid metabolism. Kyoto Encyclopedia of Genes and Genomes analysis indicated involvement in regulating active transmembrane transporter activity and cytochrome P450-mediated xenobiotic metabolism. Machine learning methods identified DUSP9 as a pivotal feature gene that was significantly upregulated in HB tumor tissues. In vitro functional assays demonstrated that DUSP9 knockdown markedly inhibited the proliferation and migration of HB cells. Additionally, western blot analysis revealed increased expression of epithelial markers and decreased expression of mesenchymal markers, along with a significant reduction in the phosphorylation of markers related to the MAPK signaling pathway. DUSP9 plays a crucial role in HB cell proliferation, migration, and epithelial-mesenchymal transition (EMT), potentially promoting tumor progression by regulating the MAPK signaling pathway.
2026-07-29 | SMAP1 promotes hepatoblastoma cell proliferation by modulating the C-Kit-activated ERK/MAPK pathway.
Hepatoblastoma (HB) is the most common pediatric liver malignancy. We investigated the role of SMAP1 in HB proliferation and its mechanism. Sixty-seven HB tissues were analyzed for SMAP1 expression via immunohistochemistry and correlated with clinical outcomes. qRT-PCR quantified SMAP1 mRNA in HB cell lines versus normal hepatocytes. SMAP1 was knocked down (siRNA/lentivirus) or overexpressed (plasmid) in HB cells; proliferation was assessed by CCK-8 and colony formation. A nude-mouse xenograft model was used to evaluate tumorigenicity. Western blotting determined C-Kit and ERK/MAPK pathway activity after SMAP1 modulation. Rescue experiments used ERK activator C16-PAF, inhibitor U0126, or C-Kit inhibitor ISCK03. SMAP1 was upregulated in HB and predicted poor prognosis. Knockdown reduced C-Kit, p-C-Kit, and p-ERK1/2, inhibited proliferation and colony formation, and suppressed xenograft growth. Overexpression produced opposite effects. U0126 reversed ERK1/2 phosphorylation and p-Rb in SMAP1-overexpressing cells, whereas C16-PAF restored ERK signaling and c-Myc/p-Rb in knockdown cells. ISCK03 blocked C-Kit/ERK activation prompted by SMAP1 overexpression. SMAP1 drives HB progression by activating C-Kit-ERK/MAPK signaling, representing a potential therapeutic target.
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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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