Cancer Stem Cells And Osteosarcoma: Opportunities And Limitations

Osteosarcoma (OS) is the most common primary bone malignancy and is a leading cause of cancer-related death in children and young adults. Combination chemotherapy developed 3 decades ago significantly improved long-term survival compared to surgery alone. However, despite notable tumor cytoreduction and remission, the 5-year survival rate has remained static at similar to 70% since, and the surviving patients have high chemoresistance with sustained risk of recurrent OS that has propensity to metastasize. After metastasis, the 5-year survival rate is abysmally low (similar to 10% to 20%). Emerging new evidence has revealed that within the heterogenous OS tumor evolves a subset of cancer stem cells with progenitor abilities that contribute to chemoresistance, tumor recurrence, and metastasis. Mechanistic insight into these cells has rekindled the hope for novel agents and treatment regimens for OS patients. In this review we discuss the recent advances towards the understanding of OS with emphasis on the functions of the cancer stem cells, microenvironment niche, genetic, epigenetic factors, and signaling pathways as well as their potential for new therapeutics.