Research progress on emerging programmed cell death pathways in osteosarcoma therapy

Abstract

Osteosarcoma is a prevalent malignant bone tumor in adolescents. For decades, clinical management has been hampered by two major challenges: chemoresistance and a high metastasis rate, resulting in persistently poor survival outcomes. Conventional therapies primarily focus on inducing apoptosis in tumor cells; however, this pathway is not always effective against osteosarcoma. Consequently, there is growing interest in alternative forms of programmed cell death (PCD) beyond apoptosis to explore novel therapeutic avenues. This review examines various emerging non-apoptotic cell death modalities, including cuproptosis, ferroptosis, disulfidptosis, pyroptosis, and PANoptosis. It delves into the mechanisms governing these processes and evaluates their translational potential in osteosarcoma. Overall, therapeutic strategies targeting these novel cell death pathways may provide new insights and approaches for research, while their clinical application remains to be validated in future studies.