Our hypothesis is that inflammation and inflammatory products (notably circulating neutrophil extracellular traps [NETs]) are causal in metastatic disease and especially in the context of surgical sepsis, and that by inhibiting NETs, the rate of progression to metastatic disease will be significantly reduced. We will use a novel model for colorectal cancer to test these hypotheses.
The aims of this project are to:
- Demonstrate intrinsic interaction between circulating tumor cells and NETs formed in response to surgery and subsequent sepsis;
- Demonstrate evidence of increased metastatic disease as a result of the inflammatory response to surgery and its complications in colorectal cancer;
- Examine whether adjunct therapy targeting NETs and sepsis is sufficient to reduce metastasis arising from surgery.
If experimental findings are consistent with our hypotheses, it would have implications for how we treat colorectal cancer, and may translate to treatment of many other malignancies.