Grant: CIHR Fellowship

Hepatoblastoma (HB) is the most common form of childhood liver malignancy. Current treatment options rely on chemotherapy for low-risk forms of HB and require additional surgery to remove the cancer for high-risk HB. New alternate treatments for liver cancer in adults often aim to disrupt signaling pathways that are associated with early stages of liver development. Currently, it is unclear whether these experimental approaches are safe for children as their livers are still developing. Our objective in this project is to find alternative treatment options that are safer for children with liver cancer. The tumor cells in HB can become either embryonal or fetal subtypes where most HB cases have a mix of both. It is important to distinguish these sub-types because they can react to treatments differently and embryonal is often the more aggressive form of HB tumor cells. We recently studied the differences on a molecular level between the fetal and embryonal HB subtypes and found that the programming to generate energy is different between fetal, embryonal, and normal liver cells. If we can selectively disrupt the energy production that specifically fuel the survival of tumor cells and minimize damage to normal cells, then we can create a treatment is more specific for pediatric patients and improve quality of life. To achieve this goal, we need to: (1)Identify the molecular machineries used for energy generation that are unique to fetal, embryonal, or normal cells and we can do this using a technology known as mass spectrometry. (2)Test if the prevention of the manufacturing of these machinery will result in specific cell starvation and death of tumor cells but not normal cells. Our studies will provide new information that can be used for novel approaches to selectively prevent HB tumor cells growth without damaging normal liver development in children.