Targeted Therapy of Osteosarcoma: A Review

Osteosarcoma (OS) is the most common primary malignant tumor, arising from mesenchymal cells of bones in children and young adults. Despite advancements in treatment, including neo-adjuvant chemotherapy and surgical resection, the prognosis for metastatic disease remains poor. This necessitates the exploration of novel targeted therapies to improve patient outcomes. Methods: This review synthesizes recent literature on targeted therapies for OS, focusing on key molecular targets and their potential therapeutic applications. We have reviewed studies that investigated various molecular pathways and their roles in OS progression and treatment. Results: Our findings identify various molecular targets with therapeutic potential in OS: ۱. Serine/Threonine Kinase Family: The mTOR pathway emerges as a crucial target in OS therapy. Inhibitors like RES-۵۲۹ and CZ۴۱۵ have shown promise in limiting OS cell growth. Also, The CDKs-inhibitor, roscovitine, showed effective responses in vitro and was able to enhance the activity of chemotherapy agents. ۲. Receptor Tyrosine Kinases (RTKs): Insulin-like Growth Factor Receptors and Vascular Endothelial Growth Factor Receptors play significant roles in OS progression. Targeting these RTKs with specific inhibitors (e.g., Apatinib) or monoclonal antibodies (e.g., cixutumumab, dalotuzumab and robatumumab) has demonstrated therapeutic potential in inhibiting OS growth and improving outcomes. ۳. P۵۳ and Its Regulators: P۵۳ mutations are common in OS, impacting therapeutic efficacy. MDM۲, a negative regulator of p۵۳, inhibitors, aims to restore p۵۳ function or mimic its activity, offering potential pathways to overcome resistance. ۴. MYC Family: MYC family genes, particularly c-MYC, are often overexpressed in OS, contributing to aggressive tumor behavior. Inhibiting MYC signaling represents a promising approach to reduce tumor growth and enhance treatment efficacy. ۵. Non-Coding RNAs (ncRNAs): Various microRNAs and long non-coding RNAs have been identified as regulators of OS progression. Targeting specific ncRNAs shows potential in modulating OS behavior and enhancing sensitivity to conventional therapies. ۶. Other Emerging Targets: Additional targets include histone demethylases (KDM۴A, KDM۶B), HMGB۱, and various signaling pathways implicated in OS progression. Inhibition of these pathways might offer novel therapeutic avenues to treat OS. Conclusion: Targeted therapies represent a promising frontier in OS treatment, focusing on the underlying molecular mechanisms driving the disease. Leveraging targeted therapies alongside traditional therapies might hold substantial promise in improving patient outcomes. Further research is crucial to translating these findings into effective clinical treatments for osteosarcoma.

کلیدواژه ها:

Osteosarcoma ، Targeted Therapy ، Molecular Target