骨肉瘤是一种罕见的原发性骨癌，呈现出多种分子畸变，凸显了其复杂性。尽管研究人员不断努力，但五年生存率的改善有限，表明当前的治疗策略不足以满足临床需求。分子谱分析的进步促进了对骨肉瘤生物学的理解，为治疗提供了广阔的前景。迫切需要开发创新方法来应对骨肉瘤的复杂挑战，最终有助于改善患者的治疗效果。这篇综述探讨了骨肉瘤和癌症易感综合征之间的关系、其体细胞基因组的复杂性以及临床上可行的改变。这篇综述涵盖了治疗策略，包括手术、化疗、免疫检查点抑制剂（ICIs）和酪氨酸激酶抑制剂（TKI）。针对多种途径的创新治疗方式，包括多靶点酪氨酸激酶、细胞周期、PI3K/mTOR 途径和 DNA 损伤修复 (DDR)，提供了有希望的干预措施。这篇综述还涵盖了有前景的途径，包括抗体药物偶联物 (ADC) 和免疫治疗策略，例如细胞因子、过继性细胞疗法 (ACT)、ICIs 和癌症疫苗。这一全面的探索有助于全面理解，为临床应用提供指导，以推进骨肉瘤的管理。版权所有 © 2024。由 Elsevier B.V. 出版。

Osteosarcoma, a rare primary bone cancer, presents diverse molecular aberrations that underscore its complexity. Despite the persistent endeavors by researchers, the limited amelioration in the five-year survival rate indicates that current therapeutic strategies prove inadequate in addressing the clinical necessities. Advancements in molecular profiling have facilitated an enhanced comprehension of the biology of osteosarcoma, offering a promising outlook for treatment. There is an urgent need to develop innovative approaches to address the complex challenges of osteosarcoma, ultimately contributing to enhanced patient outcomes. This review explores the nexus between osteosarcoma and cancer predisposition syndromes, intricacies in its somatic genome, and clinically actionable alterations. This review covers treatment strategies, including surgery, chemotherapy, immune checkpoint inhibitors (ICIs), and tyrosine kinase inhibitors (TKIs). Innovative treatment modalities targeting diverse pathways, including multi-target tyrosine kinases, cell cycle, PI3K/mTOR pathway, and DNA damage repair (DDR), offer promising interventions. This review also covers promising avenues, including antibody-drug conjugates (ADCs) and immunotherapy strategies, such as cytokines, adoptive cellular therapy (ACT), ICIs, and cancer vaccines. This comprehensive exploration contributes to a holistic understanding, offering guidance for clinical applications to advance the management of osteosarcoma.Copyright © 2024. Published by Elsevier B.V.