4th Annual Mountain West
Biomedical Engineering Conference

Peritoneal carcinomatosis, often resulting from surgical resection of abdominal tumors, represents a serious problem in cancer treatment. This condition is refractory to nearly all treatments and is nearly universally fatal. Cancer stem cells (CSCs) defined by CD133 expression have recently been shown to be highly tumorigenic and metastatic in comparison to the bulk tumor population. These cells have also been shown to be recalcitrant to conventional cancer treatments and therefore, represent a significant challenge in cancer treatment. Using enriched populations of pancreatic CSCs, we created a peritoneal carcinomatosis model of metastasis in nude mice. Our lab in conjunction with Cephalon Inc. is developing a novel inhibitor of metastasis, BAY 11-7085, which is also an NF-κB inhibitor. In vitro co-culture assays showed that this compound is capable of inducing apoptosis in re-adhering CSCs while the chemotherapeutics gemcitabine and bortezomib were not able to. Using this compound, we developed several nude mouse treatment models. One model used a single dose of BAY 11-7085 at the time of cell injection to model washing of the abdomen with drug during surgical resection of tumors. This model showed a significant difference in resulting tumor load compared to control. A second model using enriched populations of CSCs injected into nude mice and then treated periodically with BAY 11-7085 showed a significant difference in tumor load throughout a 5 month study. These results indicate BAY 11-7085 is capable of targeting CSCs and may represent a novel treatment for pancreatic cancer in the future.