"Epidemiological studies have clearly demonstrated that obesity and Type 2 diabetes are associated with an increased risk of developing common cancers including breast and colon cancer. They are also associated with increased cancer related mortality. While the mechanisms involved in this association are not yet defined, insulin resistance, hyperinsulinemia, hyperlipidemia, hyperglycemia and inflammatory cytokines are thought to be involved.
Our studies, using separate mouse models of obesity or Type 2 diabetes, have replicated the increased association of these conditions and breast cancer. We have shown that endogenous hyperinsulinemia maybe an important contributing factor in the increased cancer risk. We propose to extend these studies in a number of directions. Firstly to confirm the findings using a mouse colon cancer cell lines. We will also study metastases, using a specific breast cancer cell line that spreads to the lungs and colon cancer that spreads to the liver. In these mouse experiments we will use specific blockers to the insulin and IGF-1 receptors to determine if the role of endogenous hyperinsulinemia is indeed a major factor in metastases and through which receptor it propagates a signaling cascade. Studies on the molecular mechanisms will be carried out on cells in culture and in the tissue samples from the tumors and metastases from lung and liver.
We have also developed a model of hyperlipidemia and cancer and preliminary studies in our model suggest that, hyperlipidemia maybe another contributing factor in the connection between obesity/Type 2 diabetes and cancer and cancer metastases. This model, using breast and colon cancer, will be studied to identify the causative connection between this metabolic disorder and cancer.
Overall the plan is to identify specific causality that will help design new therapeutic agents to deal with the growing problem of cancer in obese and diabetic patients."
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