Abstract
Hepatoblastoma (HB) is the most common pediatric liver malignancy. Management of HB requires multidisciplinary efforts. The 5-year overall survival of this disease is about 80% in developed countries. Despite advances in the care of these patients, survival in recurrent or treatment-refractory disease is lower than 50%. This is due to more complex tumor biology, including hepatocellular carcinoma (HCC)-like mutations and expression of aggressive gene signatures leading to chemoresistance, vascular invasion, and metastatic spread. The current treatment protocols for pediatric liver cancer do not incorporate targeted therapies, and the ability to test these therapies is limited due to the inaccessibility of cell lines and mouse models. In this review, we discuss the current status of preclinical animal modeling in pediatric liver cancer, primarily HB. Although HB is a rare cancer, the research community has worked together to develop a range of interesting and relevant mouse models for diverse preclinical studies.
Highlights
Hepatocellular malignancies are a leading cause of cancer-related mortality in people of all ages, and children are affected by both hepatoblastoma (HB) and hepatocellular carcinoma (HCC)
PDX models is the ability to studywork tumorsto in animals that most accurately recapitulate human disease subcutaneous without the intermediate phase of in vitro growth that is thought to change cells. These models injection of fresh patient-derived cells, and patient-derived xenograft (PDX) modelsare for pediatric liver especially needed for meaningful testing of novel anti-cancer treatments
This study further demonstrated regulation of Yap-1 levels by β-Catenin at the transcriptional level, and the in vivo findings strongly showed the synergistic effect that mutant CTNNB1 and Yap-1 dual activation had on HB tumor growth [28]
Summary
Hepatocellular malignancies are a leading cause of cancer-related mortality in people of all ages, and children are affected by both hepatoblastoma (HB) and hepatocellular carcinoma (HCC). HB is the most common primary liver malignancy in children with an incidence of approximately 1.3 to 1.5 cases per million [1,2]. This disease is generally seen in patients younger than 5 years of age and is associated with prematurity, low birth weight, and non-chromosomal congenital defects [3,4,5,6]. The aggressive nature of high-risk HB concomitant with the relatively low overall disease incidence has historically prevented substantial study of more effective chemotherapy regimens and targeted therapies due to the lack of available samples. Model does not accurately recapitulate tumor microenvironment and vascularization Tumors grow as small, multifocal nodules, which makes quantifying tumor burden difficult
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