Targeting granzyme B with a novel inhibitor for the treatment of radiodermatitis
Radiodermatitis is a group of skin reactions that occur as a result of radiation therapy. It is a significant health challenge as approximately 70% of all cancer patients receive radiation therapy and approximately 95% of them experience radiodermatitis. Patients with radiodermatitis experience redness, itchiness, pain, scaling, and weeping or crusted wounds. Importantly, radiodermatitis can impede cancer treatments. Current treatments for radiodermatitis have shown limited efficacy; thus, improving our understanding of radiodermatitis and developing novel therapies are urgent needs. In our preliminary studies, we have found that the protein Granzyme B is present at very high levels in radiodermatitis skin. We also showed that Granzyme B damages components of the skin and promotes inflammation in radiodermatitis. Our proposed project will test if Granzyme B induces the symptoms of radiodermatitis and if our newly developed medication that stops Granzyme B activity can alleviate these symptoms. Findings from this study will provide further rationale to pursue inhibitors of Granzyme B as a novel treatment option for radiodermatitis.