Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. It is the fifth most common and third most lethal cancer worldwide. Most HCC patients present symptoms at advanced stages when they are no longer suitable for surgical treatments. Unfortunately, HCC is resistant to conventional radio- and chemo-therapies. Currently, there is only one FDA approved targeted therapy for advanced HCC patients but its effect is only modest. Therefore, knowledge on the molecular biology of HCC is warranted for the development of better diagnostic platforms and therapeutic regimens. Our research focuses on two emerging and fundamental aspects in HCC.
Mechanisms of Immune Evasion/ Immune therapy
Solid tumors, in addition to malignant cells, are made up of other non-malignant cell types (stromal cells). Stromal cells include fibroblasts, endothelial cells, and immune cells. Solid tumors are also embedded in a remodeled extracellular matrix (ECM). Solid tumors are constantly experiencing inflammation and temporal changes of oxygen tension. These cellular and non-cellular components provide a unique tumor microenvironment conferring malignant cells oncogenic and metastatic properties. Our research focuses on the molecular mechanisms involved in the formation of tumor microenvironment of HCC. Currently, we are investigating the clinical implications, regulations, and roles of hypoxia (oxygen deprivation) in ECM modification in HCC. We are also investigating the roles of hypoxia in stromal cell-cancer cell interaction. We are particularly interested in dissecting the recruitment mechanism of myeloid-derived suppressor cells (MDSCs), a type of immune-suppressive cells that allow HCC cells to escape immune surveillance and resist immuno-therapies.
The major difference between cancer cell and normal cell is that cancer cell growth is uncontrollable. Unlike normal differentiated cells which utilize mitochondrial oxidative phosphorylation to produce energy, cancer cells metabolize glucose by aerobic glycolysis, a phenomenon called the “Warburg Effect”. Although aerobic glycolysis is an energy-inefficient process, it advantages cancer cells to divert glucose intermediates for anabolic reactions and anti-oxidant production. Liver has many unique metabolic functions including gluconeogenesis, glycogen synthesis and storage, and blood glucose homeostasis. During the development of HCC, the metabolic machineries are extensively reprogrammed to support the insatiable nutrient requirement of HCC. Our group is investigating the signaling pathways that rewire the metabolic programs in HCC. Understanding the metabolic reliance of HCC is essential to the development of drugs that could effectively and selectively stop HCC growth. We are actively investigating drugs that could paralyze the metabolic machinery of HCC cells, making them more vulnerable to existing treatments.
Carmen Wong HKU