Deciphering the Signaling Mechanisms of Osteosarcoma Tumorigenesis

Osteosarcoma (OS) is the predominant primary bone tumor in pediatric and adolescent populations. It has high metastatic potential, with lungs being most common site of metastasis. In contrast to many other sarcomas, OS lacks conserved translocations or genetic mutations; instead, it heterogeneous abnormalities, including somatic DNA copy number alteration, ploidy, chromosomal amplification, loss gain. Unfortunately, clinical outcomes have not significantly improved over 30 years. Currently, no effective molecularly targeted therapies are available for this disease. Several genomic studies showed inactivation suppressor genes, p53, RB, ATRX, hyperactivation promoter MYC MDM2, OS. Alterations major signaling pathways, PI3K/AKT/mTOR, JAK/STAT, Wnt/β-catenin, NOTCH, Hedgehog/Gli, TGF-β, RTKs, RANK/RANKL, NF-κB been identified development Although treatment currently based on surgical excision systematic multiagent therapies, several potential development. This review focuses pathways OS, we propose a biological rationale consider novel future.