Adams Julian
Millennium Pharmaceuticals, Cambridge, Massachusetts 02139, USA.
Curr Opin Oncol. 2002 Nov;14(6):628-34. doi: 10.1097/00001622-200211000-00007.
The targeted degradation of key regulatory proteins is an essential element of cell cycle control. The proteasome plays a central role in the degradation of such proteins and has therefore become an important therapeutic target for diseases involving cell proliferation, notably cancer. This review summarizes numerous studies demonstrating that proteasome inhibition induces apoptosis and sensitizes cancer cells to traditional tumoricidal agents both and The potent and selective proteasome inhibitor, PS-341, is particularly promising from a therapeutic perspective, and it is the only such inhibitor that has progressed to clinical trials. Preliminary data indicate that the drug is well tolerated by patients with cancer, and further trials are underway to assess the safety and efficacy of proteasome inhibition in hematologic and solid tumors, both as a monotherapy and in combination with other chemotherapeutics.
关键调节蛋白的靶向降解是细胞周期调控的一个基本要素。蛋白酶体在这类蛋白质的降解中起核心作用，因此已成为涉及细胞增殖疾病（尤其是癌症）的重要治疗靶点。本综述总结了大量研究，这些研究表明蛋白酶体抑制可诱导细胞凋亡，并使癌细胞对传统肿瘤杀伤剂敏感。从治疗角度来看，强效且选择性的蛋白酶体抑制剂PS - 341特别有前景，它是唯一进入临床试验阶段的此类抑制剂。初步数据表明，癌症患者对该药物耐受性良好，目前正在进行进一步试验，以评估蛋白酶体抑制在血液系统肿瘤和实体瘤中的安全性和有效性，包括作为单一疗法以及与其他化疗药物联合使用的情况。
