Hepatoblastoma (HB)

Hepatoblastoma (HB) is the most frequent liver cancer in children. It is a malignant embryonal tumor that undergoes differentiation in several ways. At Protheragen, we focus on providing integrated diagnosis and therapeutics development services for Hepatoblastoma (HB).

Overview of Hepatoblastoma (HB)

Hepatoblastoma (HB) is the most prevalent liver cancer in children, typically diagnosed in children younger than 5, with the most common age of onset being 3 years old. This tumor of embryonic origin has a spectrum of differentiating types of tissue and is noted for its aggressive nature, including swift metastatic spread. Incidence is around 1.2 to 1.5 cases per million population yearly, and though its etiology is largely unknown, some hereditary and developmental factors are known to contribute to its pathogenesis.

Fig.1 N6-methyladenosine (m⁶A) modification core gene polymorphisms and hepatoblastoma risk. (Chen H., et al., 2021)

Pathogenesis of Hepatoblastoma (HB)

The causes of hepatoblastoma are both genetic and epigenetic factors. Some genetic syndromes like Beckwith-Wiedemann Syndrome (BWS), Familial Adenomatous Polyposis (FAP), and Hemihypertrophy significantly increase the risk of hepatoblastoma. The disorder BWS is associated with the genetic alteration of chromosome 11p15.5 and defects of 11p15.5, which increases the risk of hepatoblastoma. Also, FAP, which is known to be caused by mutations in the APC gene on chromosome 5q21-q22, increases the risk of hepatoblastoma. Moreover, some chromosomal abnormalities such as trisomy 2 and 20, along with alterations in the Wnt/β-catenin signaling pathway, are commonly seen in hepatoblastoma, which points to their important contribution to the development of the tumor.

Diagnostics Development for Hepatoblastoma (HB)

• Serum Markers: Heightened concentrations of alpha-fetoprotein (AFP) in serum are a distinguishing feature of hepatoblastoma and have a sensitivity and specificity of 98.0% and 100% respectively. Furthermore, AFP levels are of prognostic significance as well, with unfavorable prognostic outcomes associated with lower AFP levels.
• Biopsy: A definitive diagnosis requires a biopsy for histological confirmation. Biopsy samples can be obtained percutaneously, laparoscopically, or through open surgical techniques based on bleeding risk and tissue sample volume required. Immunohistochemical markers like INI1, CD44, and CD90 are markers which increasingly assist with reframing therapy strategies and predicting outcomes.

Therapeutics Development for Hepatoblastoma (HB)

• Chemotherapy
  Hepatoblastoma continues to be effectively managed with chemotherapy, especially with cisplatin-based regimens. These are the most productive ones. The Children's Oncology Group along with the other member institutions in the International Childhood Liver Tumor Strategy Group (SIOPEL), has established protocols that incorporate cisplatin with doxorubicin, vincristine, and fluorouracil. The survival outcomes have greatly improved, with the 5-year overall survival (OS) rates achieving 82% in some cases.
• Targeted Therapies
  Targeted therapies concentrate on particular molecular processes like the PI3K/Akt/mTOR and Wnt/β-catenin pathways that are related to hepatoblastoma. The use of some drugs, for example, sorafenib, an antineoplastic agent which inhibits multiple kinases, has shown some promise in hepatoblastoma. Other forms of therapeutics are also being explored, including Immunotherapy, cancer immunotherapy using monoclonal antibodies against "immune checkpoints" and CAR-T cells that recognize and respond to tumor-associated antigens.

Table 1. Clinical trials for hepatoblastoma. (Zhu L., et al., 2022)

Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.

Our Services

Advances in genetic and epigenetic research have shed light on the pathogenic mechanisms underlying HB, paving the way for the development of targeted therapy strategies. At Protheragen, we are dedicated to advancing the field of HB research through our comprehensive diagnostics and therapeutics development services.

Diagnostics Development

• Karyotype Analysis Service
• Omics Analysis Service
• Biomarker Development Service
• Artificial Intelligence Service

Therapeutic Development

• Anticancer Peptide
• Gene Therapy
• Immunotherapy
• Monoclonal Antibody
• Small Molecule Drug
• Phytotherapy
• Therapeutic Cancer Vaccine

Preclinical Research

• Pharmacodynamics Study Services
• Pharmacokinetics Study Services
• Drug Safety Evaluation Services

Disease Models

• HepT1-derived Murine Models
• LIN28B GEM Models
• myc/CTNNB1 GEM Models
• Prom1 Crerecombination GEM Models
• CTNNB1/Yap-1 Hydrodynamic Tail Vein injection/Sleeping Beauty Transposon Models

Protheragen offers customized services tailored to the specific needs of our clients, including the development of patient-derived xenograft (PDX) models, drug combination studies, and immune-oncology assays. Our team of experts works closely with clients to design and execute studies that address their unique research questions. If you are interested in our services, please feel free to contact us.

References

• Chen, Huitong, et al. "The genetic changes of hepatoblastoma." Frontiers in Oncology 11 (2021): 690641.
• Cao, Yinbiao, Shurui Wu, and Haowen Tang. "An update on diagnosis and treatment of hepatoblastoma." BioScience Trends 17.6 (2023): 445-457.
• Zhu, Li-ran, et al. "Epigenetics and genetics of hepatoblastoma: Linkage and treatment." Frontiers in Genetics 13 (2022): 1070971.

All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.