Impact of STAG2 loss on DNA Damage and Immunobiology in Ewing sarcoma
Ewing sarcoma is a cancer most often diagnosed in teenagers. We know that some changes in the make-up of Ewing tumors make them more likely to be aggressive and spread to other parts of the body. When Ewing sarcoma spreads to other parts of the body, like the lung, it is very hard to cure. Radiation is one therapy used to treat Ewing sarcoma in the lungs. Radiation can directly damage tumor cells and can also "call" immune cells into the tumor to help attack cancer cells. We have found that some types of aggressive Ewing sarcomas send out signals for immune cells to "go away." Our current work is to determine how some aggressive Ewing tumors quiet the immune system and to figure out how to turn this effect off in order to maximize the benefit of radiation for the treatment of Ewing sarcoma that has spread to the lung.
Project Goal:
The goals of our project are to 1) figure out why some Ewing sarcomas that spread to the lung tend to "quiet" the ability of the immune system to attack the tumor and 2) find immunotherapies to pair with radiation therapy in order to better treat lung metastatic Ewing sarcomas with certain genetic features. We want to improve the outcomes of teenagers diagnosed with metastatic Ewing sarcoma.
Project Update 2024:
Metastatic Ewing sarcoma continues to be difficult to treat. Our focus is studying Ewing tumors that have traveled to the lung, the most common site of metastatic disease seen in patients. We now know that Ewing tumors that lose the expression of a protein called STAG2 are more aggressive. Given their aggressive nature, it is important to understand these tumors in order to find better treatments for patients that have this type of Ewing sarcoma. We are looking at how inflammation and immune cell interactions are different in these tumors by utilizing a unique mouse model of Ewing sarcoma. We have found cytokines (proteins released during inflammation) that appear to be different (lower or missing) in Ewing tumors with STAG2 loss. We are now doing next-step experiments to verify these findings. We hope to be able to treat these tumors with agents to fix the normal inflammatory responses and make the tumors less aggressive.
