Pancreatic cancer kills just about every patient that has it. Patients are first seen with advanced disease and rarely respond to current treatments. More advanced therapies are needed to save lives. Recent studies suggest that pancreatic cancer cells are especially reliant on cellular recycling processes for growth. Mouse models of pancreatic cancer show that blocking these recycling processes can decrease the growth of tumors. These results have led to the launch of several clinical trials. However, initial results from these clinical trials show that pancreatic cancer cells stop responding. The tumors become resistant to blocking recycling pathways. We have made pancreatic cancer cells resistant to these therapies in the lab. We will use these cells to uncover better therapies to prevent resistance and increase patient survival.
Previously, research showed that these recycling processes promote tumor growth. But, in some contexts these same recycling processes can block pancreatic tumor growth. Researchers still don’t know how or when this switch happens. This dual role could contribute to the therapeutic resistance seen in patients. To study this phenomenon, I will use mini-pancreatic organs, called organoids, that can be grown in the lab. For the first time, we will be able to study the mechanisms that regulate the dual roles of cellular recycling in pancreatic cancer. Together these studies will allow us to target the tumor promoting functions of the recycling pathways while preserving the tumor blocking functions. This will prevent resistance and increase patient survival.
