Proteasome inhibitor, bortezomib, for myeloma and lymphoma
Proteasome inhibitor, bortezomib, for myeloma and lymphoma
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DOI：
10.1007/s10147-007-0695-5
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发表时间：
2007-10
影响因子：
3.3
通讯作者：
K. Tobinai
中科院分区：
文献类型：
--
作者：
K. Tobinai
Bortezomib 是一种硼酸，是一种有效的选择性蛋白酶体抑制剂。 20S蛋白酶体是细胞中存在的一种酶复合物，它降解许多细胞周期控制因子、信号转导因子、转录因子以及癌基因和抗癌基因产物，从而控制细胞增殖、分化和凋亡。硼替佐米是一种新型分子靶向剂，旨在通过选择性抑制 20S 蛋白酶体来发挥抗肿瘤作用。多发性骨髓瘤是无法治愈的 B 细胞恶性肿瘤之一，在目前的治疗方式下会持续复发，并且反复接受化疗的患者的进展持续时间会缩短。没有可用的治疗方案可以在复发后预期持久疗效；因此，需要一种具有新颖作用机制的有效疗法。在这篇综述文章中，总结了硼替佐米治疗多发性骨髓瘤的临床试验结果，包括日本 I/II 期和药代动力学/药效学研究，以及非霍奇金淋巴瘤，特别是套细胞淋巴瘤的临床试验结果。在硼替佐米治疗复发性多发性骨髓瘤的日本 I/II 期研究中，该药物显示出显着的疗效，具有可接受的毒性和独特的药代动力学/药效学特征，值得进一步研究，包括更相关的给药方案。
Bortezomib, a boronic acid, is a potent and selective proteasome inhibitor. The 20S proteasome is an enzyme complex present in cells, and it degrades many cell-cycle control factors, signal transduction factors, transcription factors, and oncogene and anti-oncogene products, thus controlling cell proliferation, differentiation, and apoptosis. Bortezomib is a novel molecular targeting agent which was designed to exhibit an antitumor effect by selectively inhibiting the 20S proteasome. Multiple myeloma is one of the incurable B-cell malignancies that continues to relapse with current treatment modalities, and the duration to progression becomes shorter in patients who repeatedly receive chemotherapy. There are no available treatment options in which durable efficacy can be expected after relapse; therefore, an effective therapy with a novel mechanism of action has been desired. In this review article, the results of clinical trials of bortezomib for multiple myeloma, including a Japanese phase I/II and pharmacokinetic/pharmacodynamic study, and those for non-Hodgkin lymphoma, especially for mantle cell lymphoma, are summarized. In the Japanese phase I/II study of bortezomib for relapsed multiple myeloma, this agent showed remarkable efficacy, with acceptable toxicities and unique pharmacokinetic/pharmacodynamic profiles, warranting further investigations, including more relevant administration schedules.