硼替佐米在多发性骨髓瘤中耐药机制的研究

第一代蛋白酶体抑制剂硼替佐米(BTZ)已广泛应用于临床,其主要通过竞争性结合蛋白酶体β5亚基、抑制蛋白酶体功能来干扰细胞内蛋白质降解过程,从而诱导肿瘤细胞凋亡.自2000年美国食品和药品监督管理局(FDA)批准BTZ用于治疗多发性骨髓瘤(MM)以来,MM患者的缓解率及长期生存率得到了明显提高,但在疾病终末期多数患者仍面临耐药复发的问题.因此,探讨BTZ耐药机制、寻找克服BTZ耐药的用药策略是MM治疗的一大挑战.本文就近年来多项关于MM中BTZ耐药机制的相关研究进展进行综述.

Resistance mechanism of bortezomib in multiple myeloma

Bortezomib (BTZ), being the first proteasome inhibitor, has been applied widely in clinic. Through combining with targeting β5 subunit/chymotrypsin-like and inhibiting the activity of proteasome reversibly, BTZ manages to inhibit intracellular degradation of protein, thus inducing apoptosis of myeloma cells. Since 2000, when BTZ was approved by Food and Drug Administration (FDA) for treatment of multiple myeloma (MM), both response rates and long-term survival time of these patients have been improved significantly. However, most patients will inevitably end up with relapse or drug resistance due to its high heterogeneity. Thus, it is of great necessity to explore the mechanism as well as overcome BTZ resistance. This review aims to summarize the current researches available on mechanisms of BTZ resistance in MM.