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[摘要]
随着新辅助化疗的广泛应用和手术技术的进展,骨肉瘤患者的5年生存率得到了很大提高,但受肿瘤细胞耐药机制和免疫逃逸的影响,目前骨肉瘤的疗效处于“瓶颈”状态。近期的研究显示,骨肉瘤细胞中存在着一些表达间充质干细胞和胚胎干细胞表面标志和表型的干细胞样肿瘤细胞,它们具有自我更新、广泛增殖的特点;同时,自骨肉瘤细胞分选出表达高水平ABCG2、能在NOD/SCID小鼠成瘤的SP细胞,显示骨肉瘤细胞耐药可能与SP细胞相关。研究针对上述标志物和降低ABCG2表达的治疗方法或药物,将有望进一步提高骨肉瘤的疗效。此外,研究主动和被动免疫疗法,以及针对Src蛋白酪氨酸激酶等靶点的靶向治疗也将为提高骨肉瘤的疗效提供新的途径。
[Key word]
[Abstract]
Abstract Great improvement has been made in the 5 year survival of patients with osteosarcoma due to application of novel chemo agent and progression in surgical techniques. However, the treatment outcome of osteosarcoma was bottlenecked by drug resistance and immuno escape mechanism. Recent studies showed that some osteosarcoma cells possess the characteristic of tumor stem cells: capable of self renewal and extensive proliferation. Meanwhile, SP cells, isolated from osteosarcoma cells, have high expression of ABCG2 and can form tumor in NOD/SCID mice, indicating that the drug resistance of osteosarcoma cells might be related to SP cells. Studies on the biomarkers of tumor stem cells and decrease of ABCG2 expression may contribute to the treatment outcome of osteosarcoma. Moreover, research on active and passive immunotherapy and Src protein tyrosine kinase targeted therapy may provide new pathways for treatment of osteosarcoma.
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