Grant: Project Grant - Priority Announcement: Pediatric Cancer Research

Chemo/radiation is standard therapy for most cancers, making the long-term consequences of radiation exposure a significant concern, particularly in childhood cancer survivors. The effects of chemo/radiation on skeletal muscle are often ignored; however, most cancer survivors experience muscle weakness and wasting due to the gradual, steady replacement of healthy muscle tissue with fibrous, fatty tissue. This decline in muscle health is irreversible and currently has no cure. Exciting new data from my lab indicate that cancer therapy reduces the number of support cells necessary for maintaining muscle. These support cells work by releasing factors that promote skeletal muscle repair and growth. Interestingly, we have determined that the essential signals normally released from these cells are lost following chemo/radiation therapy. However, a full understanding of how cancer therapy alters the function of these necessary support cells has not been tested. Thus, the overall objective of this project is to better define how cancer therapy causes dysfunction in this important support cell population in muscle. Further, we will test if replacing these support cells, or their signals can prevent the chronic, therapy-induced reduction in muscle in cancer survivors. We expect to find that chemo/radiation reduces the ability of these cells to support normal muscle growth and eventually leads to the accumulation of fatty/fibrous tissue in skeletal muscle. We further expect to discover that replacing factors produced by healthy muscle cells not exposed to chemo/radiation either directly prevents the negative long-term effects. These findings will have a significant impact on the health of Canadians because they will begin to identify novel treatments to maintain muscle quality and function in cancer survivors, which will ultimately improve their quality of life.