Ubiquitin–proteasome system as a target for anticancer treatment—an update

Yeon Jung Kim, Yeonjoo Lee, Hyungkyung Shin, Su A. Hwang, Jinyoung Park, Eun Joo Song

Research output: Contribution to journalReview articlepeer-review

8 Scopus citations

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.

Original languageEnglish
Pages (from-to)573-597
Number of pages25
JournalArchives of Pharmacal Research
Volume46
Issue number7
DOIs
StatePublished - Jul 2023

Bibliographical note

Publisher Copyright:
© 2023, The Pharmaceutical Society of Korea.

Keywords

  • Cancer
  • Deubiquitinating enzymes (DUBs)
  • E3 ligase
  • Proteasome
  • Small molecule inhibitors
  • Ubiquitin–proteasome system (UPS)

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