骨肉瘤多药耐药的研究进展

The Research Progress of Osteosarcoma Multi-resistance

骨肉瘤是临床上最常见的原发骨肿瘤,目前的主要治疗方法是新辅助化疗结合外科手术治疗。虽然随着新型化疗药物的使用,骨肉瘤患者的5年生存率有着显著提高,但仍有很多患者在应用高强度的化疗之后并没有达到预期的治疗效果,而多药耐药(MDR)就是造成骨肉瘤化疗失败的重要原因。本文从药物的摄取减少、药物的排出增加、对药物代谢的增强、DNA拓扑异构酶异常、DNA损伤修复能力增强、对细胞凋亡的抑制、Micro RNA功能异常以及外泌体引起的多药耐药的细胞间传递这几个方面对多药耐药的形成机制进行了综述。通过了解骨肉瘤多药耐药的形成机制,从而为今后逆转多药耐药,提高肿瘤对化疗药物敏感性等方面的研究提供更为广阔的思路。

Osteosarcoma is the most common primary bone tumors. At present, the main treatment of osteosarcoma is neoadju- vant chemotherapy combined with surgery. With the use of new chemotherapy drugs, the 5-year survival rate has been significantly im- proved among the patients with osteosarcoma. Howerver, many patients still can not achieve good therapeutic effects after the application of intensive chemotherapy, and multi-drug resistant is an important reason for chemotherapy failure. In this article, 8 mechanisms of MDR are introduced, including the reduction of drug absorption, the increase of drug efflux, the strengthening of drug metabolism, the abnormity of DNA TOPO II, the strengthing of base repairing, the inhibition of cell apoptosis, the disorder in the fimction of MicroRNA and the delivery of MDR by exosomes. By understanding the mechanisms of MDR in osteosarcoma, we will have a wider range of ideas in the research on reversing MDR and improving the tumor sensitivity to chemotherapy drugs.