Children's cancers are intrinsically different from tumors in adults. Whereas adult cancers are often thought to occur after the accumulation of genetic damage to replicating tissues, pediatric tumors are often thought of as occurring as a result of errors in developmental pathways, coupled with key mutational events. Because of the distinct biology driving these embryonal tumors, pediatric cancers, particularly rare ones, risk being left behind in the ongoing revolution in targeted therapy.

A second challenge faced in pediatric oncology is the treatment of rare tumors. Even the most common childhood cancers occur in only a few thousand patients in the U.S. per year. For rare tumors the numbers are smaller, making it imperative that investigators and clinicians at multiple institutions work together to improve outcomes for these tumors. Hepatoblastoma is a pediatric cancer that exemplifies these challenges. Hepatoblastoma, the most common tumor of the liver in childhood, arises from a primitive, undifferentiated cell type, the hepatoblast, and thus retains embryonal-like characteristics. Though rare in the overall population, hepatoblastoma is the most common liver tumor in children and is increasing in incidence, particularly in certain high-risk subgroups of patients such as former premature infants. Treatment of hepatoblastoma has been essentially static for the past two decades, and utilizes cytotoxic chemotherapy, usually cisplatinum, vincristine and 5-fluorouracil. Though generally effective, this regimen still fails to cure ~30% of cases of hepatoblastoma and causes significant morbidity and adverse late effects including hearing loss and renal damage. Such toxicity has a disproportionate effect on children, who even when cured face many years of post-chemotherapy disability. However, in the absence of an in-depth biological understanding of these tumors, no targeted therapy has been developed.


The overall goals of this Multi-Investigator Research Proposal is to further the understanding of the development of liver tumors, particularly hepatoblatoma and its variants, in children through a combined genomic and molecular pathology approach. The specific aims of the four interacting projects:

  • Project 1: Expression and microRNA profiling of hepatoblastoma.
  • Project 2: Genomic characterization of hepatoblastoma using massively-parallel DNA sequencing.
  • Project 3: Development of a mouse model of hepatoblastoma.

These three projects are supported by 3 cores

  • Administrative Core
  • Pathology Core
  • Bioinformatics and Biostatistics Core

Participating Research Teams

UT Health Science Center at San Antonio
Baylor College of Medicine, Houston
UT Southwestern Medical Center at Dallas