由于泛素-蛋白酶体系统（UPS）调节几乎所有的生物过程，UPS组分的失调或异常表达会导致许多病理性疾病，包括癌症。为寻找新的抗癌治疗靶点，自从FDA于2003年首次批准蛋白酶体抑制剂博特泽米治疗多发性骨髓瘤（MM）以来，UPS一直是一个活跃的研究领域。在这里，我们总结了新发现的UPS组分，包括E3泛素连接酶、去泛素酶（DUBs）和免疫蛋白酶体，它们的功能障碍导致肿瘤发生，并且从2020年开始已经在临床试验中作为抗癌治疗药物进行研究。我们深入解释了几种抑制剂的机制和效果，以更好地理解靶向UPS组分进行癌症治疗的优势。此外，我们还描述了克服一些已上市蛋白酶体抑制剂耐药性和疗效有限问题的尝试，以及一种针对UPS组分的新型PROTAC工具在抗癌治疗中的应用。© 2023. 韩国制药协会。

As the ubiquitin-proteasome system (UPS) regulates almost every biological process, the dysregulation or aberrant expression of the UPS components causes many pathological disorders, including cancers. To find a novel target for anticancer therapy, the UPS has been an active area of research since the FDA's first approval of a proteasome inhibitor bortezomib in 2003 for treating multiple myeloma (MM). Here, we summarize newly described UPS components, including E3 ubiquitin ligases, deubiquitinases (DUBs), and immunoproteasome, whose malfunction leads to tumorigenesis and whose inhibitors have been investigated in clinical trials as anticancer therapy since 2020. We explain the mechanism and effects of several inhibitors in depth to better comprehend the advantages of targeting UPS components for cancer treatment. In addition, we describe attempts to overcome resistance and limited efficacy of some launched proteasome inhibitors, as well as an emerging PROTAC-based tool targeting UPS components for anticancer therapy.© 2023. The Pharmaceutical Society of Korea.