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Author Spotlight: Unveiling the Role of TMOD3 in Platinum Resistance and Immune Infiltration in Ovarian Cancer
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Deubiquitinases in Ovarian Cancer: Role in Drug Resistance and Tumor Aggressiveness

Giovanni Luca Beretta1, Matteo Costantino1, Luca Mirra1

  • 1Molecular Pharmacology Unit, Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Amadeo 42, 20133 Milan, Italy.

International Journal of Biological Sciences
|October 21, 2024
PubMed

Insights

Deubiquitinases (DUBs) are emerging as key players in ovarian cancer drug resistance and immune suppression. Targeting DUBs offers promising therapeutic strategies for this lethal disease.

Area of Science:

  • Biochemistry
  • Oncology
  • Molecular Biology

Background:

  • Ovarian cancer is a deadly disease often diagnosed late, with platinum-based therapies frequently failing due to drug resistance.
  • Drug resistance in ovarian cancer arises from both tumor-intrinsic factors and the tumor microenvironment.
  • Deubiquitinases (DUBs), enzymes that remove ubiquitin, are increasingly recognized for their roles in cancer progression and drug resistance.

Purpose of the Study:

  • To summarize the critical role of DUBs in ovarian carcinoma.
  • To explore how DUBs contribute to drug resistance and immune suppression in ovarian cancer.
  • To provide insights into future therapeutic strategies targeting DUBs.

Main Methods:

  • Literature review and synthesis of existing research on DUBs in ovarian cancer.
  • Analysis of DUBs' involvement in DNA damage repair, apoptosis, and immune modulation.
  • Examination of specific DUBs (e.g., USP14, RPN11/PSMD14, USP1, USP8) and their mechanisms in conferring drug resistance.

Main Results:

  • DUBs influence DNA damage repair and apoptosis, processes critical for drug resistance.
  • Certain DUBs modulate T cell populations, contributing to an immunosuppressive tumor microenvironment.
  • Specific DUBs like USP14, RPN11/PSMD14, USP1, and USP8 are implicated in mechanisms driving ovarian cancer drug resistance.

Conclusions:

  • DUBs are crucial regulators of processes underlying ovarian cancer drug resistance and immune evasion.
  • DUBs are druggable targets, with inhibitors currently under development.
  • Targeting DUBs, particularly in combination therapies, presents a promising future direction for treating ovarian cancer.
Keywords:
deubiquitinasesovarian cancer, drug resistanceproteasome, deubiquitinase targeting

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