Redefining Osteosarcoma Metastases as Chronic Non-healing Lung Wounds: Implications for Developing Novel Therapies
Research Institute at Nationwide Children's Hospital
James Reinecke, MD/PhD
Young Investigator Grants
Type of Childhood Cancer:
Osteosarcoma is a bone cancer that affects children, adolescents, and young adults. Thanks to modern treatment approaches, nearly 7 out of 10 young people diagnosed with osteosarcoma survive into adulthood. Unfortunately, a significant number of patients die from osteosarcoma, most often because the osteosarcoma cells have spread to areas outside of the bone through a process called metastasis. When some cancers metastasize, they go to multiple organs throughout the body. Osteosarcoma is unique in that it largely metastasizes only to the lung. Once osteosarcoma starts to grow in the lung, there are no effective treatments to stop them from growing, which eventually leads to death. My research focuses on understanding why osteosarcoma "prefers" the lung, how osteosarcoma changes the lung to suite its needs, and how altered lung cells promote osteosarcoma survival in the lung. My work demonstrates that osteosarcoma cells induce a “scab” or wound within the lung. While most wounds heal without incident, my work demonstrates that osteosarcoma cells trick the lung into thinking there is constant injury. The lung reacts to this by depositing proteins and other factors that allow the osteosarcoma cells to survive and grow within the lung. This proposal aims to figure out how osteosarcoma cells induce this wound environment in order to find drugs that can stop the process, which would inhibit osteosarcoma growth within the lung. Therapies that prevent or treat lung metastasis could save 80% of lives lost to osteosarcoma.
The long-term goal of this Alex Lemonade Stand Young Investigator proposal is to discover therapies that are effective against osteosarcoma metastasis. The short-term goals of this proposal are to address the following three questions: 1) How do osteosarcoma cells change cells within the lung? 2) How do altered lung cells help osteosarcoma cells survive in the lung? and 3) How do cells that surround and support osteosarcoma cells change over time? My proposal will address each of these related questions using state-of-the art technologies.
Northwestern Mutual Foundation