Advances in the Molecular Biology of Chondrosarcoma for Drug Discovery and Precision Medicine

Chondrosarcomas (CSs) are generally slow-growing tumors of cartilage-producing cells, and the second most common primary bone malignancy following osteosarcoma. CSs are typically resistant to conventional chemo- and radiotherapy, and aggressive surgical resection with wide margins remains the only effective treatment option. Immunotherapies and targeted therapies in CSs have failed in clinical trials, and no prognostic biomarkers exist within the clinic. Although CSs have undergone histologic and genetic analysis, the molecular mechanisms that drive their pathogenesis and resistance are still largely unknown. A deeper understanding of the molecular biology and dysregulated pathways in CSs is essential for more efficient precision therapies. Several integrated large-scale genetic and epigenetic studies have recently been reported in CS, with several distinguished pathways holding therapeutic promise. In this review, we summarize the advances in the molecular biology of CSs, focusing on both genomic and epigenomic mechanisms as well as potential biomarkers and targets. These studies highlight several valuable clinical opportunities for earlier detection, prognostic accuracy, and therapeutic targeting that may improve patient outcomes in CSs.