Regulation of Tumor Debris Mediated Inflammation as a Therapeutic Modality in Medulloblastoma

Background:

Radiation and chemotherapy is the standard for most patients with cancer. The goal is to kill as many of the tumor cells as possible before resistance develops and the tumor stops responding. Our recent work has discovered that the release of the cellular content (cellular debris) of dead tumor cells into the tumor microenvironment provides the necessary factors that stimulate surviving tumor cells to grow.

This means that traditional therapy is a “double-edged sword”; the very treatment meant to cure your cancer is also helping it survive and grow. There are naturally occurring molecules in the body that are meant to prevent cellular debris from sending these signals; they are called resolvins and protectins because they support the removal of the cellular debris. To survive and grow, tumors must therefore trick the body into turning off the resolvins and protectins, something that they readily do. Resolvin drugs are in clinical trials for autoimmune disease (which are also thought to result from the continued stimulation of inflammation by cellular debris after an infection) and have been well tolerated to date.

Project Goal:

This proposal will evaluate the role of resolvins and protectins in pediatric medulloblastoma, which cell type in the brain regulates this process (is it the same cell type outside the brain) and test these new drugs to see if targeting this pathway can effectively reduce the stimulatory signal that tumor cells receive with therapy. This new and innovative approach could have significant implications to many pediatric and even adult tumors.