Randomized Phase II study of borteozmibEPOCH-R in Mantle cell lymphoma

蛋白酶体的小分子抑制剂硼替佐米促进细胞凋亡；这种效果似乎部分是由于防止NF-kB激活，但其确切机制尚未完全确定。此外，蛋白酶体降解除调节细胞凋亡外具有多种细胞功能的蛋白质（例如细胞周期蛋白）。虽然先前的研究显示硼替佐米在淋巴瘤（包括MCL39）中的临床前景，但在应答者和无应答者中调节的关键信号通路尚未表征。由于硼替佐米通过抑制蛋白体降解起作用，预计其主要作用将在蛋白质水平上观察到。改善MCL的生存是很重要的，可以通过新的靶向药物来实现。

The small molecule inhibitor of the proteasome, bortezomib, promotes apoptosis; this effect appears to be due in part to prevention of NF-kB activation, but the precise mechanisms have not been fully established38. Furthermore, the proteasome degrades proteins with a wide variety of cellular functions other than regulation of apoptosis (e.g. cell cycle proteins). While previous studies have shown clinical promise of bortezomib in lymphoma, including MCL39, the key signaling pathways modulated in responders and non-responders have not been characterized. Because bortezomib acts by inhibiting proteosomal degradation, its principal effects are expected to be observed at the protein level. Improving the survival of MCL is important and may be achieved with new targeted agents.