The latest clinical trials of osteosarcoma: A review

Osteosarcoma (OS) is the most common primary bone malignancy with a high propensity for metastasis and local invasion. The annual incidence rate is ۱.۷ per ۱۰۰,۰۰۰ in children under ۱۰ years of age, ۸.۲ per ۱۰۰,۰۰۰ in patients aged ۱۰-۱۹ years, and the ۵-year survival rate is ۶۰-۷۰%. In comparison, the survival rate for patients with metastatic OS is only ۱۹-۳۰%. Current treatment options for OS include surgery, neoadjuvant chemotherapy, and postoperative chemotherapy. However, treatment outcomes are unsatisfactory. In addition, the survival rate of patients with metastasis has not increased significantly in recent decades. In order to find a more effective therapy, many scientists around the world have conducted various types of research. Therefore, we have reviewed and summarized the latest clinical trials on osteosarcoma. Methods: Multiple databases were searched, including PubMed, Google Scholar, Web of Science, Scopus, etc. Using the terms “clinical trials”, “osteosarcoma”, and “treatment”, relevant articles published since ۲۰۲۰ were selected and reviewed. Results: According to the research, the isphosphonate zoledronic acid inhibits bone resorption by suppressing osteoclast differentiation. A trial of ۳۱۸ patients showed no clinical benefit for patients who received zoledronic acid along with chemotherapy compared with chemotherapy alone. In addition, a study on tyrosine kinase receptors (RTKs) showed that RTKs irregularities are associated with chemotherapy resistance, tumor neovascularization, and metastasis. Tyrosine kinase inhibitors (TKIs) inhibit the catalytic activity of RTKs by interfering with the binding of their intracellular domain to ATP or other substrates. Results showed that key RTKs for osteosarcoma treatment may include vascular endothelial growth factor receptors (VEGFRs) and rearranged during transfection (RET). However, inhibition of one type of RTKs is not effective in the treatment of osteosarcoma. Nevertheless, combination therapy using different selective (or single-target) TKIs in osteosarcoma will be the future trend. Another research was conducted on mycophenolate mofetil, which is a prodrug of mycophenolic acid (MPA), a potent inhibitor of inosine monophosphate dehydrogenase (IMPDH). In some cancers with upregulated IMPDH, MPA may possess anti-cancer activity; inhibition of IMPDH could result in decreased cell proliferation and viability. In vivo experiments showed that mice treated with mycophenolate mofetil inhibited tumor growth and lung metastasis of osteosarcoma. However, the clinical use of mycophenolate mofetil requires further investigation. Conclusion: OS is the most common primary bone tumor, primarily affecting young adults. However, the ۵-year survival of osteosarcoma patients has not improved over the past decades. As a result, several trials have been conducted, including the use of zoledronic acid, TKIs, and mycophenolate mofetil. The use of zoledronic acid with chemotherapy showed no improvement, as did the use of TKIs, which also failed due to the need to inhibit several relevant RTKs simultaneously to achieve a breakthrough in osteosarcoma treatment. The mycophenolate mofetil approach is more promising, as it has demonstrated an effective cure in mice. Therefore, it suggests a therapeutic potential against osteosarcoma in humans. Nevertheless, further studies should be conducted to achieve a safe treatment for OS.

کلیدواژه ها:

Osteosarcoma (OS) ، metastasis ، clinical trial ، treatment