Osteosarcoma mechanobiology and therapeutic targets.

Osteosarcoma (OS) is the one of the most common primary tumors of bone with less than a 20% 5-year survival rate after the development of metastases. OS is highly predisposed in Paget's disease (PD) of bone, and both have common characteristic skeletal features due to rapid bone remodeling. OS prognosis is location dependent which further emphasizes the likely contribution of the bone microenvironment in its pathogenesis. Mechanobiology is the phenomenon when mechanical cues from the changing physical microenvironment of bone are transduced to biological pathways through mechanosensitive cellular components. Mechanobiology-driven therapies have been used for curbing tumor progression by direct alteration of the physical microenvironment or inhibition of metastasis-associated mechanosensitive proteins. This review emphasizes the contribution of mechanobiology to OS progression, and sheds light on current mechanobiology-based therapies and potential new targets for improving disease management. Additionally, the variety of 3D models currently used to study OS mechanobiology are summarized.