Proteasome Inhibitors and Their Potential Applicability in Osteosarcoma Treatment

SIMPLE SUMMARY: Bone cancer has seen minimal benefits in therapeutic options in the past 30 years. Proteasome inhibitors present a new avenue of research for the treatment of bone cancer. Proteasome inhibitors impair the function of the proteasome, a structure within the cell that removes unwanted and misfolded proteins. Bone cancer cells heavily rely on the proteasome to properly function and survive. Impairing the proteasome function can have detrimental consequences and lead to cell death. This review provides a thorough summary of the in vitro, in vivo, and clinical research that has explored proteasome inhibitors for the treatment of bone cancer. ABSTRACT: Osteosarcoma (OS) is the most common type of bone cancer, with ~30% of patients developing secondary/metastatic tumors. The molecular complexity of tumor metastasis and the lack of effective therapies for OS has cultivated interest in exploiting the proteasome as a molecular target for anti-cancer therapy. As our understanding towards the behavior of malignant cells expands, it is evident that cancerous cells display a greater reliance on the proteasome to maintain homeostasis and sustain efficient biological activities. This led to the development and approval of first- and second-generation proteasome inhibitors (PIs), which have improved outcomes for patients with multiple myeloma and mantle cell lymphoma. Researchers have since postulated the therapeutic potential of PIs for the treatment of OS. As such, this review aims to summarize the biological effects and latest findings from clinical trials investigating PI-based treatments for OS. Integrating PIs into current treatment regimens may better outcomes for patients diagnosed with OS.