Studying how liver-tumor interaction contributes to the development and drug resistance of pediatric and adult liver cancer
The liver is the body’s largest internal organ and carries out over 500 distinct roles. To protect its vital functions, the liver has a built-in damage-response system that involves an immense diversity of cell types. In the context of cancer, the variety of these responses results in a dynamic tumor-liver interaction that relates to tumor progression. We ultimately want to broaden the focus of liver cancer research beyond a limited examination of just the tumor. The goal of our laboratory is to understand how liver-tumor interaction contributes to the development of liver cancer and subsequent drug response in children and adults. Deepening our understanding of how the tumor and liver interact will help us better predict patient prognosis and treatment response.
Given the liver’s vast cell diversity, multitude of functions, and essential roles in drug metabolism, there is much to learn about this large organ in the context of cancer. Yet, a lack of liver cancer models that incorporate liver-tumor interaction makes the comprehensive understanding of liver tumorigenesis challenging. Our main goal is to build liver cancer models that include cellular components from both the tumor and the liver so we can study the contribution of their interaction to disease progression and drug response.
Developing liver cancer models to investigate tumor-host interaction
With the increasing appreciation of the tumor microenvironment’s role in cancer progression and drug resistance, studying how the tumor and host interact may be key to understanding disease state and drug response. Our work expands the focus of existing liver cancer models to new research platforms that incorporate more environmental players in order to study their systemic response to liver cancer development.
We are most interested in late-stage disease when the disease has spread and effective treatment options are limited. Building models of late-stage liver cancers, in both children and adults, is imperative. Most of our work concentrates on hepatoblastoma, a very rare—but the most common—liver cancer in children. We also study cholangiocarcinoma, a rare liver cancer that affects mainly adults. Discovering how the liver reacts to disease development will help us understand how the host-organ reaction contributes to tumor progression and treatment resistance in liver cancer patients with advanced diseases.
We conduct in vitro co-culture work in observation of how different liver cell types interact and change tumor cell behavior. Our goal is to place liver cancer cells in a simplified liver environment composed of mainly hepatocytes—the basic functional units of the liver—and gradually add other cell types to discern how they individually and systemically contribute to a disease state. Our current work with these models shows the hepatic stellate cells play an important role in inducing tumor dissemination in both hepatoblastoma and cholangiocarcinoma. Our characterization of the liver environment also reveals a drastic immune response in the tumor-surrounding liver of cholangiocarcinoma patients. A future goal is to focus on these immune components—macrophages, T cells, B cells, and neutrophils—and add them into our model system to understand their contribution to tumor behavior.
Treatment response of different cell components
In a secondary focus of our laboratory, we examine how host liver cells impact liver cancer cells’ response to drug treatments. Understanding their systemic response aids in our comprehension of how tumor-liver interaction contributes to final drug response and outcomes in liver cancer patients. Using in vitro cell co-culture models, we will study these component-level cellular responses to treatment and then validate them in in vivo models.
Our research benefits from the exceptional resources and strong collaborative spirit of St. Jude. From the solid tumor program to pathology to bioinformatics, collaboration and teamwork defines our laboratory’s approach. The exploration of science and the urge to unearth new discoveries with avid curiosity drives us forward as we work to fulfill the St. Jude mission.