MULTIMODAL APPROACH AND THERAPEUTIC ADVANCES IN THE TREATMENT OF OSTEOSARCOMA

Abstract

Osteosarcoma is the most prevalent primary malignant bone neoplasm, occurring predominantly in children and adolescents. It is characterized by the production of immature osteoid matrix and by an extremely unstable and heterogeneous genomic profile. Although standard chemotherapy (MAP) has increased the five-year survival rate to 60–70% in localized disease, the prognosis for metastatic or recurrent disease remains stagnant at approximately 20%. The complexity of treatment lies in the genetic instability and the intricate interaction with the bone microenvironment, which acts as a vital support for tumor growth and dissemination, promoting therapeutic resistance. This study is a narrative literature review that sought to synthesize contemporary scientific evidence regarding the multimodal approach and therapeutic advances in combating osteosarcoma. The findings reveal that overcoming chemoresistance requires the integration of innovative strategies, such as nanotechnology for active and targeted drug delivery, using specific ligands (e.g., bisphosphonates or folate), which maximize drug concentration at the tumor site and mitigate systemic toxicity. In immunotherapy, the focus is on manipulation of the cGAS-STING axis and repolarization of tumor-associated macrophages (TAMs) to the M1 phenotype, as observed with mifamurtide, aiming to reverse microenvironmental immunosuppression. Other approaches include multiple kinase inhibitors (MKIs), such as sorafenib and regorafenib, and unconventional administration routes, such as inhaled chemotherapy for pulmonary metastases. In conclusion, the effective integration of these innovative strategies (nanotechnology, immunomodulation, and targeted therapies) represents the future of osteosarcoma oncology, offering renewed hope for prolonging progression-free survival and overall survival in patients.