Deciphering the Signaling Mechanisms of Osteosarcoma Tumorigenesis.
Bikesh K NiralaTaku YamamichiJason T YusteinPublished in: International journal of molecular sciences (2023)
Osteosarcoma (OS) is the predominant primary bone tumor in the pediatric and adolescent populations. It has high metastatic potential, with the lungs being the most common site of metastasis. In contrast to many other sarcomas, OS lacks conserved translocations or genetic mutations; instead, it has heterogeneous abnormalities, including somatic DNA copy number alteration, ploidy, chromosomal amplification, and chromosomal loss and gain. Unfortunately, clinical outcomes have not significantly improved in over 30 years. Currently, no effective molecularly targeted therapies are available for this disease. Several genomic studies showed inactivation in the tumor suppressor genes, including p53 , RB , and ATRX, and hyperactivation of the tumor promoter genes, including MYC and MDM2 , in OS. Alterations in the major signaling pathways, including the PI3K/AKT/mTOR, JAK/STAT, Wnt/β-catenin, NOTCH, Hedgehog/Gli, TGF-β, RTKs, RANK/RANKL, and NF-κB signaling pathways, have been identified in OS development and metastasis. Although OS treatment is currently based on surgical excision and systematic multiagent therapies, several potential targeted therapies are in development. This review focuses on the major signaling pathways of OS, and we propose a biological rationale to consider novel and targeted therapies in the future.
Keyphrases
- copy number
- genome wide
- signaling pathway
- mitochondrial dna
- dna methylation
- pi k akt
- transcription factor
- cell proliferation
- epithelial mesenchymal transition
- small cell lung cancer
- young adults
- stem cells
- squamous cell carcinoma
- oxidative stress
- magnetic resonance
- gene expression
- induced apoptosis
- mental health
- human health
- bone loss
- transforming growth factor
- circulating tumor
- nucleic acid
- bone mineral density
- inflammatory response
- immune response
- risk assessment
- toll like receptor
- postmenopausal women
- cell free
- genome wide identification
- replacement therapy