Grant: Project Grant

Obesity is associated with an elevated risk of developing 13 cancer types, and an elevated risk of dying from 14 cancer types. In Canada, 24% of adults are obese and another 36% are overweight. In addition, 20% of people with a normal body weight are 'metabolically obese', meaning they have similar health risks as obese people, even though they appear healthy. Consequentially, obesity now rivals smoking tobacco as the leading preventable risk factor for cancer mortality, estimated to be responsible for up to 20% of all cancer-related deaths in adults. Most cancer deaths are caused by metastasis (cancer spread), yet we lack a strong understanding of how obesity regulates cancer metastasis. In previously published work, we discovered that obesity enhances cancer metastasis to the lungs through its effects on immune cells. We observed similar effects on immune cells in the liver, suggesting that obesity may also enhance liver metastasis. The biggest source of liver metastasis is colorectal cancer (CRC), which is the 2nd leading cause of cancer-related deaths in Canada. Obesity increases the risk of death from CRC by >40% in men and >30% in women, and we suspect it does this by enhancing liver metastasis. In new experiments, we have found that CRC liver metastasis is enhanced in mouse models of obesity. This occurs in part through the effects of obesity on specific cells of the immune system (monocytes and T cells). The objective of this proposal is to determine how monocytes and T cells regulate obesity-associated liver metastasis. We hypothesize that therapies that target these immune cells will reduce cancer progression in obese hosts. Given the prevalence of obesity and its association with cancer mortality, our research will uncover therapeutic opportunities for patients predisposed to have poorer outcomes.