Cancer is a problem of uncontrolled cell growth. Either too many new cells are being born or not enough old cells are dying. Cellular senescence is a normal aging process in which cells stop growing. However, these cells remain metabolically active and secrete factors to attract immune cells and increase inflammation. This process occurs naturally during aging due to different types of stress that build up over time. Senescence was first thought to protect against cancer since it prevents new cells from being made. In fact, many drugs currently used to treat human cancer patients block tumor growth by turning on senescence. However, more recent studies have shown that some tumor cells can eventually escape this process and start growing again. Cells that exit senescence may even grow faster and spread more easily than before. Given these new findings about the ‘dark side’ of senescence, there has been growing interest in using anti-aging drugs to treat cancer. However, this process is complex and has been difficult to study in the lab. We created a new mouse model of adrenocortical carcinoma (ACC), which is a deadly cancer that starts in the adrenal gland and has no effective treatments. Our model develops adrenal cancer, but only after an extended period of senescence. This model provides a unique opportunity to study the relationship between aging and cancer. Using this system, our goal is to (1) study the long-term effects of senescence on tumor growth, and (2) test anti-aging drugs as cancer therapy.
Location: Huntsman Cancer Institute -
Proposal: Cellular Senescence as a Pro-Tumorigenic Process and Therapeutic Target