Abstract:

Osteosarcoma (OS), the most common primary bone malignancy, predominantly affects children and adolescents, with poor prognosis in advanced or metastatic cases. Originating from osteoblasts, OS is characterized by rapid proliferation, local invasion, and a high propensity for lung metastasis. It is classified as primary (central or surface) or secondary when arising from preexisting conditions. Despite advances in chemotherapy and surgery, the long-term survival rate for patients with metastatic or recurrent OS remains poor, emphasizing the need for novel therapeutic approaches. Phytomedicine, derived from plant-based compounds, has garnered attention for its potential in targeting OS molecular pathways. Phytochemicals such as curcumin, resveratrol, and epigallocatechin gallate (EGCG) exhibit therapeutic effects by modulating key pathways, including Wnt/β-catenin, PI3K/AKT/mTOR, and MAPK/ERK, which are crucial for OS cell migration, proliferation, and survival. These compounds inhibit angiogenesis, promote apoptosis, and reduce metastasis by regulating the epithelial-to-mesenchymal transition (EMT). Additionally, they induce reactive oxygen species (ROS), trigger autophagy, and disrupt cellular signaling, effectively killing OS cells. Emerging studies highlight the potential of phytomedicines to enhance current treatments and improve patient outcomes by offering less harmful and more effective options. This review explores the molecular mechanisms underlying OS and evaluates phytomedicine's role in developing innovative therapies. By integrating genetic, molecular, and clinical profiles, these findings provide valuable insights for advancing OS diagnosis and management, offering hope for more sustainable and effective treatment strategies.

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