Validating a Mouse Model of Alveolar Rhabdomyosarcoma

Background

Rhabdomyosarcoma is a cancer of connective tissue that has features of skeletal muscle and it is the most common connective cancer of childhood and adolescence. While the pediatric cancer community has made great strides in treating rhabdomyosarcoma and providing more supportive care during therapy, there are still some patients in high risk groups who do not survive their disease. In particular, children with the alveolar type of rhabdomyosarcoma, whose tumors express a genetic mutation called PAX3-FOXO1, have a 5-year survival of less than 10% when their tumors are metastatic.

Our laboratory has been trying for years to understand how and why the PAX3-FOXO1 mutation contributes to such a poor outcome. To this end, we have developed both cell and mouse-based models of alveolar rhabdomyosarcoma and we have recently discovered that silencing of a tumor-suppressing signaling pathway called Hippo appears to contribute to more aggressive disease.

Project Goal

In this project, we will scrutinize a new mouse model of alveolar rhabdomyosarcoma made to both express PAX3-FOXO1 and silence the Hippo pathway. We will carefully examine the tumors that arise in this model. We will also make immortal cell lines out of them so that we can work with them in the future to identify the characteristics underlying their aggressive nature. We hope that our findings will someday be translated to new treatments.