Bortezomib: proteasome inhibition as an effective anticancer therapy.
Bortezomib: proteasome inhibition as an effective anticancer therapy.
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DOI：
10.1517/14796694.1.2.161
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发表时间：
2005-04
期刊：
影响因子：
3.3
通讯作者：
P. Richardson;C. Mitsiades
中科院分区：
文献类型：
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作者：
P. Richardson;C. Mitsiades
抑制蛋白酶体会破坏细胞内的蛋白质稳态，从而导致细胞凋亡，这是一种在恶性肿瘤细胞中优先观察到的现象。Bortezomib(VELCADE)是一种一流的蛋白酶体抑制剂，专门用于抗肿瘤药物。它的第一个适应症是治疗至少接受过两次治疗并在之前的治疗基础上取得进展的复发性骨髓瘤患者，部分是基于第二阶段试验所显示的活动程度。一项III期试验的中期分析显示，在复发性骨髓瘤患者中，硼替佐米比大剂量地塞米松有显著的疗效优势。正在进行临床开发，以研究其作为单一疗法和联合方案治疗非霍奇金淋巴瘤、实体瘤和骨髓瘤早期表现的活性。
Inhibition of the proteasome results in disruption of protein homeostasis within the cell that can lead to apoptosis, a phenomenon preferentially observed in malignant cells. Bortezomib (VELCADE) is a first-in-class proteasome inhibitor developed specifically for use as an antineoplastic agent. Its first indication, for the treatment of relapsed myeloma in patients who have received at least two prior treatments and progressed on their previous treatment, was based in part on the magnitude of activity demonstrated in Phase II trials. An interim analysis of a Phase III trial demonstrated a significant efficacy advantage of bortezomib over high-dose dexamethasone in patients with relapsed myeloma. Clinical development is ongoing to investigate its activity as monotherapy and in combination regimens for the treatment of non-Hodgkin's lymphoma, solid tumors, and early presentations of myeloma.