Kim, Yeon Jung Lee, Yeonjoo Shin, Hyungkyung Hwang, SuA Park, Jinyoung Song, Eun Joo 2024-01-19T09:04:00Z 2024-01-19T09:04:00Z 2023-08-24 2023-07 0253-6269 https://pubs.kist.re.kr/handle/201004/113498 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. English 대한약학회 Ubiquitin-proteasome system as a target for anticancer treatment-an update Article 10.1007/s12272-023-01455-0 1 Archives of Pharmacal Research, v.46, no.7, pp.573 - 597 Archives of Pharmacal Research 46 7 573 597 N scie scopus kci ART002986286 001042474700001 2-s2.0-85166980348 Chemistry, Medicinal Pharmacology & Pharmacy Pharmacology & Pharmacy Review MAINTENANCE THERAPY MDM2 INHIBITOR CANCER DISCOVERY POTENT DEGRADATION CARFILZOMIB DISULFIRAM PATHWAY USP15 Ubiquitin-proteasome system (UPS) E3 ligase Deubiquitinating enzymes (DUBs) Proteasome Cancer Small molecule inhibitors