RANKL inhibitors for osteosarcoma treatment: hope and caution

Chen and collaborators propose RANKL blockade for the treatment and prevention of aggressive RANKL-overexpressing osteosarcoma (OS) in humans. Here we comment the main findings, putative applications and concerns. OS is the most common primary bone cancer, which occurs primarily in children and adolescents, severely affecting survivors’ quality of life. Current treatment for newly diagnosed OS includes three main components: preoperative chemotherapy, surgical resection, and postoperative chemotherapy (1). This strategy has improved the outcome of patients with localized OS. However, patients with advanced, metastatic, and recurrent OSs continue to experience a quite poor prognosis. After aggressive treatment with both surgery and chemotherapy, the 5-year survival rate for OS patients with localized disease is about 65%, whereas it is less than 20% for patients with metastases. The use of adjuvant chemotherapy provides no survival advantage for patients with pulmonary metastases (2). So that, it is of particular importance to develop molecularly targeted therapy to treat patients with this metastatic bone malignancy, on the basis of in-depth understanding of signaling mechanisms involved in OS tumorigenesis.