骨肉瘤肺转移的作用机制及其临床治疗策略

Mechanisms and clinical therapeutic strategies for pulmonary metastasis in osteosarcoma

摘要:

骨肉瘤是最常见的骨原发性恶性肿瘤，具有高度的局部侵袭和远处转移倾向，且优先向肺组织转移，其高转移潜能与低生存率相关。然而，原发肿瘤切除后骨肉瘤肺转移和局部复发的作用机制尚无详细的综述报道。现依据骨肉瘤肺转移基本机制的最新研究进展，探讨手术创伤、免疫、血管生成、癌基因、转移前微环境等相关因素在促进骨肉瘤肿瘤细胞迁移、侵袭和肺转移中的作用，并在此基础上，探讨骨肉瘤目前的临床治疗策略，以期未来的研究中能探索出更加安全有效的治疗手段。该综述为降低骨肉瘤肺转移的发生和改善治疗效果提供了一些新的治疗方案。

Abstract:

Osteosarcoma, the most common primary malignant bone tumor, is characterized by aggressive local invasion and a high propensity for distant metastasis, particularly to the lungs. Pulmonary metastasis is a critical determinant of poor prognosis, with 5-year survival rates plummeting below 20% in metastatic cases. Despite advances in primary tumor resection, the molecular and microenvironmental mechanisms driving post-surgical pulmonary recurrence and metastasis remain insufficiently elucidated. This review synthesizes recent advances in understanding the multifactorial pathogenesis of osteosarcoma pulmonary metastasis, emphasizing the roles of surgical trauma-induced inflammatory cascades, immune evasion (PD-1/PD-L1 axis dysregulation), angiogenic reprogramming, oncogenic drivers (e.g., MYLK overexpression), and pre-metastatic niche formation in promoting tumor cell migration, invasion, and pulmonary colonization. Furthermore, we critically evaluate current clinical strategies, including immune checkpoint inhibitors, tyrosine kinase inhibitors, and metastasis-targeted therapies, while highlighting emerging approaches such as microenvironment modulation and epigenetic therapeutics. By integrating mechanistic insights with translational evidence, this review proposes a framework for developing combinatorial therapies to suppress metastatic progression and improve patient outcomes.