Ito Shigeki
Hematology & Oncology, Department of Internal Medicine, Iwate Medical University School of Medicine, Yahaba-cho 028-3695, Japan.
Cancers (Basel). 2020 Jan 22;12(2):265. doi: 10.3390/cancers12020265.
Use of proteasome inhibitors (PIs) has been the therapeutic backbone of myeloma treatment over the past decade. Many PIs are being developed and evaluated in the preclinical and clinical setting. The first-in-class PI, bortezomib, was approved by the US food and drug administration in 2003. Carfilzomib is a next-generation PI, which selectively and irreversibly inhibits proteasome enzymatic activities in a dose-dependent manner. Ixazomib was the first oral PI to be developed and has a robust efficacy and favorable safety profile in patients with multiple myeloma. These PIs, together with other agents, including alkylators, immunomodulatory drugs, and monoclonal antibodies, have been incorporated into several regimens. This review summarizes the biological effects and the results of clinical trials investigating PI-based combination regimens and novel investigational inhibitors and discusses the future perspective in the treatment of multiple myeloma.
在过去十年中，蛋白酶体抑制剂（PIs）的使用一直是骨髓瘤治疗的主要手段。许多蛋白酶体抑制剂正在临床前和临床环境中进行研发和评估。首个蛋白酶体抑制剂硼替佐米于2003年获得美国食品药品监督管理局批准。卡非佐米是新一代蛋白酶体抑制剂，它以剂量依赖的方式选择性且不可逆地抑制蛋白酶体酶活性。伊沙佐米是首个研发的口服蛋白酶体抑制剂，对多发性骨髓瘤患者具有强大的疗效和良好的安全性。这些蛋白酶体抑制剂与其他药物，包括烷化剂、免疫调节药物和单克隆抗体，已被纳入多种治疗方案。本综述总结了基于蛋白酶体抑制剂的联合治疗方案和新型研究性抑制剂的生物学效应及临床试验结果，并讨论了多发性骨髓瘤治疗的未来前景。
