Bone sarcomas: from biology to targeted therapies

Abstract

Primary malignant bone tumours, osteosarcomas, and Ewing sarcomas are rare diseases which occur mainly in adolescents and young adults. With the current therapies, some patients remain very difficult to treat, such as tumour with poor histological response to preoperative CT (or large initial tumour volume for Ewing sarcomas not operated), patients with multiple metastases at or those who relapsed. In order to develop new therapies against these rare tumours, we need to unveil the key driving factors and molecular abnormalities behind the malignant characteristics and to broaden our understanding of the phenomena sustaining the metastatic phenotype and treatment resistance in these tumours. In this paper, starting with the biology of these tumours, we will discuss potential therapeutic targets aimed at increasing local tumour control, limiting metastatic spread, and finally improving patient survival.

Figure 1

Targets and therapies in preclinical and clinical development in children and adolescent bone sarcomas. (A) Ewing sarcomas. (B) Osteosarcomas. The different colors described the current clinical development of the drugs. (Red) Preclinical: EW and OS; (Orange) Phase I: all paediatric studies; (Blue) Phase II: specific EW, OS, bone tumours; (Green) Phase III: specific EW and/or OS; (Black) Phase I or II in adults: all solid tumours. *17-AAG is an HSP90 inhibitor which targets client proteins involved in all tumour characteristics.

Figure 2