Bone sarcomas: pathogenesis and new therapeutic approaches

Bone sarcomas include a very large number of tumor types belonging to the family of primary malignant bone tumors and originate from bone. Osteosarcoma, Ewing's sarcoma and chondrosarcoma are the three main sarcomas diagnosed in humans and despite their scarcity, sarcomas are characterized by a relatively high morbidity and mortality, especially in children and adolescents. Bone sarcomas exhibit highly heterogeneous histologic and molecular profiles; their morphology is one of the key aspects of their identification. With the exception of Ewing's sarcoma, which is related to a chromosomal translocation between the EWS gene and a gene from the ETS family, or to specific inherited syndromes (e.g., p53, Rb), the causes of most bone sarcomas are not fully understood. Recent published work demonstrates the key relationship between sarcoma cells and their microenvironment, opening a new era for understanding the pathogenesis of and advancing therapy for bone sarcomas, which are the focus of this Perspective.