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Deubiquitinating enzymes: Promising targets for drug resistance

Journal

DRUG DISCOVERY TODAY
Volume 27, Issue 9, Pages 2603-2613

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.drudis.2022.06.009

Keywords

Deubiquitinating enzymes; Drug resistance; DNA repair; Apoptosis; Signaling pathways; Transcription factors; Therapeutic targets

Funding

  1. National Natural Science Foundation of China [U21A20420, 82173836]
  2. Westlake Laboratory (Westlake Laboratory of Life Sciences and Biomedicine)

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This article focuses on the significant role of DUBs in the development of drug resistance and the potential application of DUB inhibitors in combination therapies to overcome drug resistance.
Drug resistance to chemotherapy and molecularly targeted therapies is a current challenge in cancer treatments. The underlying mechanisms of resistance to cytotoxic chemotherapeutics and to drugs that target a specific molecule are not understood completely. In recent years, emerging evidence has frequently suggested that the dysregulation of deubiquitinating enzymes (DUBs) plays important roles in the development of drug resistance. We focus on the molecular mechanisms through which DUBs enable cancer cells to escape cell death and survive when exposed to a variety of anti-cancer drugs. Furthermore, this review summarizes the potential application of DUB inhibitors in combination therapies to overcome drug resistance.

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