College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea.
Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, Kentucky.
Transl Res. 2018 Aug;198:1-16. doi: 10.1016/j.trsl.2018.03.002. Epub 2018 Mar 26.
Over 2 decades ago, the proteasome was considered a risky or even untenable therapeutic target. Today, proteasome inhibitors are a mainstay in the treatment of multiple myeloma (MM) and have sales in excess of 3 billion US dollars annually. More importantly, the availability of proteasome inhibitors has greatly improved the survival and quality of life for patients with MM. Despite the remarkable success of proteasome inhibitor therapies to date, the potential for improvement remains, and the development and optimal use of proteasome inhibitors as anticancer agents continues to be an active area of research. In this review, we briefly discuss the features and limitations of the 3 proteasome inhibitor drugs currently used in the clinic and provide an update on current efforts to develop next-generation proteasome inhibitors with the potential to overcome the limitations of existing proteasome inhibitor drugs.
20 多年前，蛋白酶体曾被认为是一个风险较高甚至难以实现的治疗靶点。如今，蛋白酶体抑制剂已成为多发性骨髓瘤（MM）治疗的主要药物，年销售额超过 30 亿美元。更重要的是，蛋白酶体抑制剂的出现极大地提高了 MM 患者的生存率和生活质量。尽管迄今为止蛋白酶体抑制剂疗法取得了显著的成功，但仍有进一步改善的空间，开发和优化蛋白酶体抑制剂作为抗癌药物的研究仍在继续。在这篇综述中，我们简要讨论了目前临床上使用的 3 种蛋白酶体抑制剂药物的特点和局限性，并介绍了开发新一代蛋白酶体抑制剂的最新进展，这些抑制剂有可能克服现有蛋白酶体抑制剂药物的局限性。
