Dissecting Ewing Sarcoma On-Chip for Better Therapeutics

Dr. Yuan Gao, Ph.D. – Case Western Reserve University - School of Medicine, Cleveland, OH

Ewing sarcoma is a rare and aggressive cancer that primarily affects the bones or soft tissues of children and young adults. For patients whose cancer has spread or returned, survival rates remain below 30% at five years. Current treatments like chemotherapy and radiation often fail in these high-risk cases. While new approaches like CAR T cell therapy have transformed care for some cancers, they’ve been ineffective in Ewing sarcoma, largely due to a poor understanding of how the tumor interacts with its surroundings, especially the bone marrow environment that supports tumor growth and immune evasion. To address this, we developed a 3D model called Sarcoma-on-a-Chip that mimics the human bone marrow. This miniaturized living system includes tumor cells along with immune cells, blood vessels, and bone-forming support cells. It enables us to study how Ewing sarcoma behaves in a realistic, human-like setting. Using this platform, we will 1)identify genes that help the tumor survive in the bone marrow using CRISPR gene-editing tools, and 2) investigate how the tumor suppresses immune responses. Early findings show that Ewing sarcoma disrupts immune cell function and creates an immune-suppressive environment. This project will uncover new vulnerabilities in Ewing sarcoma and guide the development of more effective therapies, with the ultimate goal of improving outcomes for children with this devastating cancer.