Grants Search Results

Rhabdomyosarcoma (RMS) is a cancer with features of skeletal muscle, and the most common soft connective tissue cancer of childhood. The alveolar variant of RMS (abbreviated ARMS) is particularly hard to cure. If we could figure out which proteins in ARMS cancer cells work together to drive this cancer, we might also be able to figure out which are good drug targets. A common genetic error in ARMS is the mutant protein PAX3-FOXO1, which turns on cellular programs that cause ARMS cells to keep dividing. However, PAX3-FOXO1 is not a good drug target, and it does not work alone – it physically interacts with other proteins that carry out its cancer-causing instructions. Here, Dr. Linardic and colleagues will use a sophisticated new method to identify proteins in PAX3-FOXO1’s cellular neighborhood, a rapid screening technology to figure out which are most crucial to ARMS, then use models of ARMS to see which of the proteins might be the best drug targets. Importantly, this project will be carried out by three research teams with unique but complementary skills working together, united in a mission to find new therapies for this difficult-to-cure cancer.

Rhabdomyosarcoma is an aggressive childhood cancer that often arises in muscle. Because of the poor survival, researchers are searching for genes underlying this cancer, with the hope of blocking them. A research scientist who studies how normal muscle forms found that a gene called MEST helps in defining muscle cell precursor identity. Dr. Linardic's lab had noticed that in rhabdomyosarcoma, MEST was highly expressed, suggesting that maybe MEST tricks cells into constantly growing. This project focuses on learning how MEST contributes to rhabdomyosarcoma, and how to block it.

Alveolar rhabdomyosarcoma is an aggressive childhood cancer that often arises in muscle. It contains a DNA error which drives cells to divide when they shouldn't, resulting in cancer. Dr. Linardic has discovered one targetable protein that is controlled by this DNA error. Her work aims to understand how this protein and the DNA error associated with Alveolar Rhabdomyosarcoma are related, and whether the protein she discovered will be a useful drug target.