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Deubiquitinating enzymes: Promising targets for drug resistance

Fujing Ge1, Yuekang Li1, Tao Yuan1

  • 1Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.

Drug Discovery Today
|June 27, 2022
PubMed

Insights

Drug resistance to cancer therapies is a major challenge. Dysregulation of deubiquitinating enzymes (DUBs) promotes cancer cell survival, and DUB inhibitors may offer new combination treatments.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Drug resistance to chemotherapy and targeted therapies remains a significant obstacle in cancer treatment.
  • The precise molecular mechanisms driving resistance to cytotoxic and molecularly targeted drugs are not fully elucidated.
  • Emerging research increasingly implicates the dysregulation of deubiquitinating enzymes (DUBs) in the development of cancer drug resistance.

Purpose of the Study:

  • To investigate the molecular mechanisms by which deubiquitinating enzymes (DUBs) contribute to cancer cell survival under anti-cancer drug treatment.
  • To review the role of DUBs in mediating resistance to various anti-cancer agents.
  • To explore the therapeutic potential of DUB inhibitors, particularly in combination therapies, for overcoming drug resistance.

Main Methods:

  • This review synthesizes current scientific literature.
  • Focuses on molecular mechanisms of DUBs in drug resistance.
  • Summarizes findings on DUB inhibitor applications.

Main Results:

  • Deubiquitinating enzymes (DUBs) play a critical role in enabling cancer cells to evade apoptosis and survive exposure to diverse anti-cancer drugs.
  • Dysregulated DUB activity is a key factor in the development of resistance to both conventional chemotherapy and targeted therapies.
  • Specific DUBs have been identified as crucial mediators of resistance pathways.

Conclusions:

  • Deubiquitinating enzymes (DUBs) are pivotal in facilitating cancer cell survival and promoting drug resistance.
  • Targeting DUBs presents a promising strategy to overcome resistance to existing cancer treatments.
  • The application of DUB inhibitors in combination therapies holds significant potential for enhancing the efficacy of anti-cancer treatments.
Keywords:
ApoptosisDNA repairDeubiquitinating enzymesDrug resistanceSignaling pathwaysTherapeutic targetsTranscription factors

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