Osteosarcoma mechanobiology and therapeutic targets

Abstract

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

Role of WTAP in Cancer: From Mechanisms to the Therapeutic Potential

“…Osteosarcoma is one of the most common orthopedic malignancies, with a 5-year survival rate of less than 20% after developing metastases [ 133 ]. Elevated WTAP in osteosarcoma is associated with poor prognosis and is an independent prognostic risk factor for patients with osteosarcoma [ 134 ].…”

Themed issue: ‘New avenues in cancer prevention and treatment’

“…The subject of the physical micro‐environment and its effects on bone cancer development (i.e., mechanobiology) and the efficacy of treatments, along with novel mechanobiology‐driven therapies, is discussed by Shoaib et al (2022). Survival of patients with osteosarcoma (i.e., bone cancer) seems to depend on tumour location and thus bone structure, micro‐environment and physical properties.…”

“…Survival of patients with osteosarcoma (i.e., bone cancer) seems to depend on tumour location and thus bone structure, micro‐environment and physical properties. Shoaib et al (2022) describe in detail the physical micro‐environment in osteosarcoma emphasizing potential mechanotransductive targets that could change the bone mechanobiology and affect treatment outcomes. However, to study the interactions between biology and micro‐environment, appropriate 3D models are needed that are well summarized by Shoaib et al (2022).…”

“…Shoaib et al (2022) describe in detail the physical micro‐environment in osteosarcoma emphasizing potential mechanotransductive targets that could change the bone mechanobiology and affect treatment outcomes. However, to study the interactions between biology and micro‐environment, appropriate 3D models are needed that are well summarized by Shoaib et al (2022). Increasing knowledge about novel targets, such as signalling pathways disrupted in osteosarcoma, has led to the development of inhibitors including small‐molecule compounds that could improve the efficacy of first‐line cytotoxic treatments, such as doxorubicin and cisplatin.…”

“…Identifying such targets must be followed by exploring their biological functions that can depend on post‐translational modifications, presence of distinct interactors, cellular location and many other factors that might be unique to individual patients (Buoso et al, 2022; Healy et al, 2022; Tucker & Zorn, 2022). Increasing knowledge on specific cancer drivers could be investigated as a potential tool to develop novel strategies in overcoming specific cancer hallmarks, such as stemness, GTPase activity‐driven cancers and EMT (Tucker & Zorn, 2022) and to design novel agents that precisely target cancer drivers (e.g., Ras in Ras‐mutated tumours) (Healy et al, 2022) as well as the tumour micro‐environment (Shoaib et al, 2022). Furthermore, establishing bridges between different fields, including epigenetics and epitranscriptomics, and commonly regulated processes could be the future in additional applications of existing therapeutics and achieving effective and more durable outcomes (Berdasco & Esteller, 2022).…”