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 ∼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 (∼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.
*Department of Orthopaedics, Emory School of Medicine, Decatur, GA
†Center for Molecular Oncology, University of Connecticut School of Medicine, Farmington, CT
The authors declare that they have nothing to disclose.
For reprint requests, or additional information and guidance on the techniques described in the article, please contact Abul Arif, PhD, at or by mail at Department of Orthopaedics, Emory School of Medicine, 1670 Clairmont Road, Decatur, GA 30033. You may inquire whether the author(s) will agree to phone conferences and/or visits regarding these techniques.
Online date: September 24, 2019