HepT1-derived murine models of high-risk hepatoblastoma display vascular invasion, metastasis, and circulating tumor cells

Woodfield, Sarah E.; Mistretta, Brandon; Patel, Roma H.; Ibarra, Aryana M.; Fisher, Kevin E.; Sarabia, Stephen F.; Gandhi, Ilavarasi; Reuther, Jacquelyn; Starosolski, Zbigniew; Badachhape, Andrew; Epps, Jessica; Zorman, Barry; Shah, Aayushi; Larson, Samuel R.; Srivastava, Rohit; Shi, Yan; Espinoza, Andres F.; Whitlock, Richard S.; Holloway, Kimberly; Roy, Angshumoy; Sumazin, Pavel; Ghaghada, Ketan B.; López‐Terrada, Dolores; Gunaratne, Preethi H.; Vasudevan, Sanjeev A.

doi:10.1242/bio.058973

Cited by 3 publications

(6 citation statements)

References 27 publications

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“…Furthermore, mutations in the TERT gene, specifically in the promoter region, were detected in several older patients ( 9 ). Beyond these, a range of other gene mutations in HB were identified, including ARID1A, ITPR2, APC, TP53, CX3CL1, A2ML1, CEP164 and EP300 ( 10 – 12 ). Moreover, comprehensive genomic profiling revealed alterations in genes such as ERBB4, MDM4, FBXW7, SRC, and BRCA2 due to mutations, amplification, or loss.…”

Section: Resultsmentioning

confidence: 99%

Summary of biological research on hepatoblastoma: a scoping review

Wang,

Lao,

Jiang

et al. 2024

Front. Pediatr.

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BackgroundHepatoblastoma is the most prevalent primary hepatic malignancy in children, comprising 80% of pediatric hepatic malignancies and 1% of all pediatric malignancies. However, traditional treatments have proven inadequate in effectively curing hepatoblastoma, leading to a poor prognosis.MethodsA literature search was conducted on multiple electronic databases (PubMed and Google Scholar). A total of 86 articles were eligible for inclusion in this review.ResultThis review aims to consolidate recent developments in hepatoblastoma research, focusing on the latest advances in cancer-associated genomics, epigenetic studies, transcriptional programs and molecular subtypes. We also discuss the current treatment approaches and forthcoming strategies to address cancer-associated biological challenges.ConclusionTo provide a comprehensive summary of the molecular mechanisms associated with hepatoblastoma occurrence, this review highlights three key aspects: genomics, epigenetics, and transcriptomics. Our review aims to facilitate the exploration of novel molecular mechanisms and the development of innovative clinical treatment strategies for hepatoblastoma.

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Section: Resultsmentioning

confidence: 99%

Summary of biological research on hepatoblastoma: a scoping review

Wang,

Lao,

Jiang

et al. 2024

Front. Pediatr.

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“…Patients with relapsed HB remain difficult to treat given limited therapeutic options and the lack of definitive risk stratification data 1‐4 . This is secondary to the rarity of the disease and limited clinical and biological data from patients that can contribute to large data sets, such as that our center was able to provide 1‐3 .…”

Section: Discussionmentioning

confidence: 99%

“…Patients with relapsed HB remain difficult to treat given limited therapeutic options and the lack of definitive risk stratification data. 1 , 2 , 3 , 4 This is secondary to the rarity of the disease and limited clinical and biological data from patients that can contribute to large data sets, such as that our center was able to provide. 1 , 2 , 3 Our study shows that the addition of surgical resection to medical management plays a critical role in salvaging patients with relapsed HB.…”

Section: Discussionmentioning

confidence: 99%

“… 1 , 2 , 3 , 4 This is secondary to the rarity of the disease and limited clinical and biological data from patients that can contribute to large data sets, such as that our center was able to provide. 1 , 2 , 3 Our study shows that the addition of surgical resection to medical management plays a critical role in salvaging patients with relapsed HB. In addition, we demonstrated that PRETEXT IV stage disease alone was predictive of disease relapse for patients treated in our center.…”

Section: Discussionmentioning

confidence: 99%

“…Hepatoblastoma (HB) remains the most common liver malignancy in children. 1 , 2 The overall survival (OS) for these patients has significantly improved with the implementation of platinum‐based chemotherapy regimens and surgical advancements. 3 , 4 However, relapsed disease remains a major cause of mortality.…”

Section: Introductionmentioning

confidence: 99%

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Navigating relapsed hepatoblastoma: Predictive factors and surgical treatment strategy

Espinoza,

Patel,

Shetty

et al. 2023

Cancer Medicine

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ObjectiveHepatoblastoma (HB) is the most common primary hepatic malignancy in childhood. Relapse occurs in more than 50% of high‐risk patients with a high mortality due to ineffective salvage therapies. The purpose of this study is to identify risk factors for relapsed HB and predictors of survival in a single tertiary referral center.MethodsA retrospective chart review showed 129 surgically treated HB patients from October 2004 to July 2020. Of the cohort, 22 patients presented with relapsed HB. Relapse was defined as re‐appearance of malignancy after 4 weeks of normalized AFP and disappearance of all tumors on imaging.ResultsPatients with relapsed HB had a 5‐year overall survival (OS) of 45.4% compared to 93.1% in those without relapse (p = 0.001). When comparing PRETEXT IV, microvascular invasion, metastatic disease, and age on multivariate logistic regression, only PRETEXT IV was an independent risk factor for relapsed HB with an OR of 2.39 (95% CI: 1.16–4.96; p = 0.019). Mixed epithelial and mesenchymal HB (12/19, 63.2%) was the most common histology of primary tumors while pure epithelial HB (13/15, 86.6%) was the most common relapsed histology. Combination of surgical and medical therapy for relapsed disease was predictive of survival with an HR of 16.3 (95% CI: 1.783–149.091; p = 0.013) compared to only chemotherapy.ConclusionsThis study demonstrates that PRETEXT IV staging is an independent predictor of relapsed disease. The most common relapsed histology was epithelial, suggesting a potential selection or resistance of this component. Surgical resection is a critical component of multimodal therapy for relapsed HB.

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First person – Sarah Woodfield

2022

Biology Open

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First Person is a series of interviews with the first authors of a selection of papers published in Biology Open, helping early-career researchers promote themselves alongside their papers. Sarah Woodfield is first author on ‘ HepT1-derived murine models of high-risk hepatoblastoma display vascular invasion, metastasis, and circulating tumor cells’, published in BiO. Sarah is assistant professor of surgery at Baylor College of Medicine and the Texas Children's Hospital in Houston, investigating the high-risk features of hepatoblastoma, including primarily metastasis and chemoresistance, with the overall goal of better understanding these characteristics in order to target them with novel inhibitors to improve patient outcomes.

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HepT1-derived murine models of high-risk hepatoblastoma display vascular invasion, metastasis, and circulating tumor cells

Cited by 3 publications

References 27 publications

Summary of biological research on hepatoblastoma: a scoping review

Summary of biological research on hepatoblastoma: a scoping review

Navigating relapsed hepatoblastoma: Predictive factors and surgical treatment strategy

First person – Sarah Woodfield

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