Ewing sarcoma occurs in the bone and soft tissue, most often in adolescents. Chemotherapy drugs are part of the standard care for cancer patients, and increasing delivery of chemotherapy specifically to the tumor is likely to make the chemotherapy work better. Chemotherapy is delivered to the tumor by the blood vessels, but tumor blood vessels do a poor job of delivering chemotherapy throughout the tumor. Reorganizing blood vessels to make them deliver chemotherapy more effectively has been demonstrated to increase patient survival in patients with glioblastoma, breast cancer, and even Ewing sarcoma, but there is not yet a good way to make the blood vessels work better without causing more t...

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Ewing sarcoma occurs in the bone and soft tissue, most often in adolescents. Chemotherapy drugs are part of the standard care for cancer patients, and increasing delivery of chemotherapy specifically to the tumor is likely to make the chemotherapy work better. Chemotherapy is delivered to the tumor by the blood vessels, but tumor blood vessels do a poor job of delivering chemotherapy throughout the tumor. Reorganizing blood vessels to make them deliver chemotherapy more effectively has been demonstrated to increase patient survival in patients with glioblastoma, breast cancer, and even Ewing sarcoma, but there is not yet a good way to make the blood vessels work better without causing more toxicity. Our studies suggest that remodeling blood vessels in Ewing sarcoma will make chemotherapy work more effectively. Here, we propose to use moderate aerobic exercise as a method for remodeling blood vessels in tumors in mice. We and others have performed exercise interventions with pediatric cancer patients and found that patients can safely exercise. We expect that exercise will cause more chemotherapy to get into the tumor, making it more effective. We aim to understand the pathways that control tumor blood vessel development, and the response of blood vessels to exercise, in order to identify the most therapeutically relevant method for increasing delivery of chemotherapy to the tumor. If successful, we will demonstrate that moderate aerobic exercise can be used in combination with chemotherapy to increase the anti-tumor effect. Further, we will identify new targets on the tumor blood vessels that can be modulated with drugs, for use in patients who cannot exercise. This work is important because exercise is a low-cost, low-risk method with numerous other benefits that may now be used to enhance the chemotherapy that is already used to treat Ewing sarcoma patients.

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