Systemic strategies for osteosarcoma: advances and future directions

Abstract

Osteosarcoma is a common and aggressive bone cancer in children and adolescents, typically affecting the long bones during growth spurts. Treatment involves a combination of surgery, chemotherapy, and radiotherapy. Although surgery has become more limb-preserving, the overall prognosis remains challenging, with a 5-year survival rate of 60-70% for localized disease and much lower for advanced stages. Chemotherapy is the mainstay treatment; however, it can cause severe side effects. Targeted therapies (e.g., IGF-1R inhibitors, TKIs) and immunotherapy (e.g., checkpoint inhibitors, CAR-T therapies) are promising areas of research that aim to attack cancer cells more precisely with lower toxicity. Other novel approaches, such as gene therapy and drug delivery systems, are being explored. With continued research and development of new therapies, we hope to significantly improve the outlook of patients with osteosarcoma in the future.

Keywords: Chemotherapy; Epigenetic modifications; Immunotherapy; Osteosarcoma; Targeted therapies; Viral therapy.

Fig. 1

Development and progression of osteosarcoma. Osteosarcoma is an aggressive malignant neoplasm. It typically arises in the metaphyseal region of long bones. Immature osteoblast differentiation forms the atypical hyperplasia, which converts into malignant tumor cells. This tumor cell further gets metastasized to other organs, specifically lung followed by other bone sites. This phenomenon of metastasis results in the tumor progression and development of drug resistance

Fig. 2

Current advancement in therapies for the treatment of osteosarcoma