The biology of metastases in pediatric sarcomas

In the treatment of pediatric solid tumors, the presence or development of metastatic disease carries a universally poor prognosis. In fact, most cancer deaths result from metastases rather than primary tumor growth. Although the poor outcome associated with metastatic disease has been known for some time, an understanding of the processes that allow a cancer to disseminate is only now beginning to be understood. In order for a cancer to spread beyond its local site, a complex series of events must be undertaken that must allow the cancer not only to travel into and through the circulation but also prevent elimination of these cells by the host, as well as promote growth at the metastatic site. This review presents a current model of these processes. Some of the key molecular factors influencing their development are outlined in the context of this model. We present recent advances in our understanding of metastases, especially as they relate to experimental therapies and possible molecular targets of future therapies. Finally, we discuss progress being made in our ability to study metastases and expectations for the future.