Assistant Professor, University of Massachusetts Chan Medical School
Defining the role of a novel electron transport chain metabolite in pancreatic cancer growth and immune suppression
Overview
Aim: Treatment/Therapy
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies, in large part due to the fact that it does not respond well to standard treatments. Immunotherapy has revolutionized cancer treatment in other cancer types, but pancreatic cancer remains resistant to current therapies that target the immune system. A promising way to enhance response to current immunotherapies is to find new molecules that recruit tumor-killing immune cells to the local tumor environment.
In our Hirshberg Foundation Seed Grant project, we will address this unmet clinical need by investigating the ability of a novel metabolite, Rhodoquinone, to suppress pancreatic cancer growth by reinvigorating an anti-tumor immune response. Rhodoquinone was recently discovered by our labs and rewires the electron transport chain during hypoxic (low oxygen) conditions. Its role in cancer is completely unexplored until now. Using models of pancreatic cancer, we show that Rhodoquinone blocks the growth of PDAC tumors by increasing a specialized type of immune cell that kills cancer cells. Our collaborators have synthesized a synthetic Rhodoquinone analog, and we will test its ability to combine with current immunotherapy approaches to determine new immune-boosting drug combinations for pancreatic cancer patients. Thus, we will gain mechanistic insights into how the immune system attacks pancreatic tumor cells and provide preclinical evidence for a new therapeutic metabolite for PDAC patients.
