蛋白酶体抑制剂bortezomib治疗多发性骨髓瘤的作用机制和临床试验

The mechanism of action and clinic trials of bortezomib in multiple myeloma

蛋白酶体是细胞调节信号的中心通道,可以降解和活化多种调节蛋白;蛋白酶体抑制剂可通过抑制催化中心活性,阻断大量调节蛋白的降解,引起细胞内信号系统的紊乱和超负荷,导致细胞生长的抑制,最终使肿瘤进展过程延缓甚至停滞。Bortezomib作为第一个选择性的蛋白酶体抑制剂在多发性骨髓瘤(MM)中有良好的治疗反应率和较少的毒副作用,近年来得到广泛研究。

Bortezomib is a modified dipeptidyl boronic acid. Bortezomib is a reversible inhibitor of 26S proteasome, a large protein complex that degrades ubiquitinated proteins. The ubiquitinproteasome pathway plays an essential role in regulating the intracellular concentration of specific proteins, thereby maintaining homeostasis within the cells. Inhibition of the proteasome pathway by bortezomib prevents the degradation of these intracellular proteins, affecting multiple signaling cascades within cells. This disr...