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Bortezomib for multiple myeloma.

机译：硼替佐米用于多发性骨髓瘤。

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摘要

The ubquitin-proteasome pathway is a key regulator of homeostasis within cells, degrading misfolded or redundant proteins, and also those involved in mediating transcription, cell-cycle progression and apoptosis. Inhibition of the 26S proteasome results in accumulation of such proteins and ultimately leads to cell death. Malignant cells are more susceptible to proteasome inhibition due to their higher proliferation rates, protein production and their dependence on anti-apoptotic molecules for cell survival. Bortezomib has recently gained European Commission approval for the treatment of relapsed multiple myeloma on the basis of clinical trials demonstrating its efficacy, tolerability and superiority to high-dose dexamethasone. Preclinical data demonstrates the ability to synergise with other chemotherapeutic agents and overcome drug resistance, and hence combination studies are underway. This review describes the pharmacology, toxicity, preclinical and clinical activity of bortezomib, predominantly in the setting of multiple myeloma.
机译：泛素-蛋白酶体途径是细胞内稳态的关键调节剂，降解错误折叠或多余的蛋白质，以及参与介导转录，细胞周期进程和细胞凋亡的蛋白质。 26S蛋白酶体的抑制导致此类蛋白质的积累，并最终导致细胞死亡。恶性细胞由于其较高的增殖速率，蛋白质产生以及对细胞存活的抗凋亡分子的依赖性，因此更容易受到蛋白酶体的抑制。硼替佐米最近已在临床试验的基础上获得了欧洲委员会的批准，用于治疗复发性多发性骨髓瘤，证明其疗效，耐受性和优于大剂量地塞米松。临床前数据证明了与其他化学治疗剂协同作用并克服耐药性的能力，因此正在进行联合研究。这篇综述描述了硼替佐米的药理学，毒性，临床前和临床活性，主要用于多发性骨髓瘤的治疗。

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