FCF is pleased to announce that we have awarded Yasemin Sancak, PhD, of the University of Washington a grant to study the metabolic implications and targetability of mitochondrial calcium signaling in FLC. Dr. Sancak’s lab studies mitochondria, the “powerhouses of the cell” that produce most of a cell’s energy. Dysfunctional mitochondria are linked to various diseases, including neurodegenerative disorders, cardiovascular diseases, cancer, and many metabolic syndromes.

Fibrolamellar carcinoma (FLC) is characterized by a large number of abnormal mitochondria. Currently, the significance of these mitochondrial changes in FLC is not well understood. However, FLC tumors often show resistance to chemotherapy-induced cell death as well as changes in the urea cycle in which mitochondria play a key role. FLC patients also frequently suffer from hyperammonemia as a consequence of those changes in tumor metabolism. These factors indicate that FLC’s abnormal mitochondria may be playing a significant role in the biology of the disease.

FLC mitochondria also appear swollen and contain calcium phosphate crystals, which indicate that FLC mitochondria contain excess calcium. Such increases in calcium levels could be a cause of the mitochondrial dysfunction and the major metabolic changes observed in FLC. The goal of this project is to further understand these calcium dependencies and determine if they create a cancer vulnerability that can be targeted to selectively kill FLC cells.