Deciphering the Signaling Mechanisms of Osteosarcoma Tumorigenesis

被引:12
|
作者
Nirala, Bikesh K. [1 ]
Yamamichi, Taku [1 ]
Yustein, Jason T. [1 ]
机构
[1] Emory Univ, Aflac Canc & Blood Disorders Ctr, Atlanta, GA 30322 USA
关键词
osteosarcoma; signaling pathways; oncogenes; tumor suppressors; immunotherapy; PROMOTES TUMOR PROGRESSION; WNT/BETA-CATENIN; RECEPTOR ACTIVATOR; LUNG METASTASIS; MESENCHYMAL TRANSITION; INHIBITS PROLIFERATION; CISPLATIN RESISTANCE; CELL-PROLIFERATION; TYROSINE KINASE; POOR-PROGNOSIS;
D O I
10.3390/ijms241411367
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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/& beta;-catenin, NOTCH, Hedgehog/Gli, TGF-& beta;, RTKs, RANK/RANKL, and NF-& kappa;B 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.
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页数:18
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