Osteosarcoma: Basic science and clinical implications

With the advent of chemotherapy, the treatment for osteosarcoma has made significant progress. However, this progress has slowed in recent years, leaving approximately 30% to 40% of patients who will do poorly. Research has been focused on identifying these patients early and elucidating new pathways that serve as targets for therapy. Microarray analysis is providing new means for patient risk stratification and identifying new molecules that may serve as therapeutic targets. Newly identified genes that are important for growth and development, such as the WNT/LRP5 pathway, are being investigated for their role in osteosarcoma. Chemokines may play a role in stimulating the invasiveness and homing of metastatic disease. Cytoskeletal proteins such as ezrin reveal their critical role in promoting tumor metastasis. Genes involved oncogenesis and apoptosis in other malignant tumors are being evaluated, such as Her-2/neu and Fas. Studies of osteosarcoma cells under a pressurized environment may yield important clues about tumor proliferation and responses to chemotherapy. With lessons learned from other cancers and improved molecular techniques, osteosarcoma will eventually reveal much of its secrets, yielding new ways to categorize patients and treat this disease more effectively.