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Updated: Jun 23, 2026
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Tropomodulin 3 Overexpression as a Marker for Platinum Resistance and Immune Infiltration in Ovarian Cancer
Published on: August 2, 2024
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
Summary
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.
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