Bone Cancer: Diagnosis and Treatment Principles.

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Abstract

[Indexed for MEDLINE] 3. Crit Rev Oncol Hematol. 2026 Feb;218:105075. doi: 10.1016/j.critrevonc.2025.105075. Epub 2025 Dec 12. Chondrosarcoma: Clinical behavior, molecular mechanisms, and emerging therapeutic strategies. Agulnik M(1), Wilky BA(2), Thorpe SW(3), Zuckerman LM(4). Author information: (1)Department of Medicine, Division of Medical Oncology, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA. Electronic address: mark.agulnik@med.usc.edu. (2)Department of Medicine, Division of Medical Oncology, University of Colorado School of Medicine, Aurora, CO, USA. (3)Department of Orthopedics, University of Colorado School of Medicine, Aurora, CO, USA. (4)Department of Orthopaedic Surgery, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA. Chondrosarcoma is the second most common primary malignant bone tumor. While the overall 5-year survival rate is approximately 70-75 %, high-grade tumors and aggressive chondrosarcoma subtypes are associated with a particularly poor prognosis. Wide surgical resection remains the standard treatment for localized disease and can be curative; however, effective therapies for unresectable or metastatic chondrosarcoma are needed. Preclinical research and analyses of patient tumor samples have identified several molecular mechanisms driving chondrosarcoma development and progression, including mutations in isocitrate dehydrogenases types 1 and 2 (IDH1/2) and TP53, hyperactivation of protumorigenic signaling pathways, and programmed cell death ligand 1 (PD-L1) expression. This review explores chondrosarcoma subtypes, diagnostic approaches, prognostic factors, and molecular alterations, followed by a discussion of current and emerging treatment strategies. Emphasis is placed on clinical trials investigating targeted therapies or immunotherapies for advanced chondrosarcoma, including inhibitors of IDH1/2 and multiple kinases, death receptor 5 agonism, and other potential new therapeutic approaches. Copyright © 2026 The Authors. Published by Elsevier B.V. All rights reserved. DOI: 10.1016/j.critrevonc.2025.105075