Abstract
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.
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Data availability
The datasets used and/or analysed during the current study available from the corresponding author on reasonable request.
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This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Ministry of Science and ICT (2019R1A2C2004052), and Korea Basic Science Institute (National Research Facilities and Equipment Center) grant funded by the Ministry of Education (2021R1A6C101A442)
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Kim, Y.J., Lee, Y., Shin, H. et al. Ubiquitin–proteasome system as a target for anticancer treatment—an update. Arch. Pharm. Res. 46, 573–597 (2023). https://doi.org/10.1007/s12272-023-01455-0
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DOI: https://doi.org/10.1007/s12272-023-01455-0