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Tropomodulin 3 Overexpression as a Marker for Platinum Resistance and Immune Infiltration in Ovarian Cancer
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USP18 Impacts Cisplatin Resistance in Ovarian Cancer Cells by Modulating DNA Repair

Cristina Corno1, Matteo Costantino1, Pietro Pettinari1

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

International Journal of Biological Sciences
|June 22, 2026
PubMed

Insights

Deubiquitinases (DUBs) are enzymes involved in cancer. Researchers found USP18, a DUB, is crucial for cisplatin resistance in ovarian cancer by affecting DNA repair.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Deubiquitinases (DUBs) are increasingly recognized for their roles in cancer development.
  • Platinum-based therapies are standard for ovarian cancer, but drug resistance limits their effectiveness.
  • Identifying novel factors driving platinum resistance is critical for improving patient outcomes.

Purpose of the Study:

  • To identify deubiquitinases (DUBs) essential for the survival of cisplatin-resistant ovarian cancer cells using a CRISPR/Cas9 screen.
  • To elucidate the role of USP18 in mediating resistance to platinum-based chemotherapy in ovarian cancer.

Main Methods:

  • CRISPR/Cas9 screens targeting the DUB family.
  • Preclinical pharmacology, RNA sequencing, and proteomic analyses.
  • In vivo studies in mice and in vitro assays including surface plasma resonance.

Main Results:

  • USP18 was identified as a key survival factor in cisplatin-resistant ovarian cancer cells.
  • Elevated USP18 mRNA and protein levels were observed in resistant cell lines.
  • USP18 inhibition or knockout sensitized cells to cisplatin, impairing DNA damage repair and reducing tumor growth in mice.

Conclusions:

  • USP18 is a novel mediator of cisplatin resistance in ovarian cancer, primarily through modulation of DNA repair pathways.
  • Targeting USP18 presents a potential therapeutic strategy to overcome platinum resistance in ovarian cancer.
Keywords:
CRISPR-Cas9USP18cisplatindeubiquitinasesdrug-resistanceovarian carcinoma

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