Grant: CIHR Fellowship

Liver cancer is the sixth most prevalent cancer globally, and even after conventional treatments like surgery, chemotherapy, and radiation therapy, secondary tumors can form and lead to poor survival times for patients. This tumor recurrence can be attributed to dormancy, in which a small subset of cells within the tumor become dormant cancer cells that enter an inactive, non-proliferative state which allows them to evade cancer treatments that target rapidly proliferating cells. Dormant tumor cells can reawaken unpredictably to proliferate, leading to distant metastases and recurrence at secondary tumor sites. While the mechanism of liver cancer dormancy is not well understood, biophysical signals in the tumor microenvironment (TME, i.e. tumor surroundings) can lead to shifts between dormancy and reawakening. We aim to elucidate how these signals mediate liver cancer dormancy. We will develop novel engineering tools and advanced experimental systems to recapitulate realistic features of the liver TME, enabling us to study them systematically in the lab. Liver cancers are associated with comorbidities like fibrosis, which stiffens liver tissues and alters the biomechanical and biochemical properties of the TME. Tumor growth induces compression on cells and tumor cells secrete excessive molecular factors into their surroundings, thereby altering the fluid properties within tissues, which in turn impact cancer migration, morphologies, proliferation, and behavior. We will therefore interrogate tissue structures/architectures, mechanical compression, and fluid properties as TME biophysical signals to determine their impact on dormant capable and incapable liver cancer cells. Identifying unique characteristics of dormant capable tumor cells in a realistic tumor setting will provide a key step toward targeting them and eliminating dormancy and liver tumor relapse.