ArticleOncotarget2017
The combined effect of USP7 inhibitors and PARP inhibitors in hormone-sensitive and castration-resistant prostate cancer cells.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
45 citing papers in PubMed, 74 citations in OpenAlex.
- Antagonistic Ubiquitin Switching by USP7 and RNF40 Orchestrates KDM6A Homeostasis to License Coronavirus Susceptibility.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Non-Coding RNA Biomarkers in Prostate Cancer: Evidence Mapping and In Silico Characterization.Life (Basel, Switzerland) · 2026Article
- Emerging roles of USP7 in tumor immune evasion, metabolic reprogramming, and therapeutic resistance.Frontiers in immunology · 2026Review
- USP7 promotes temozolomide resistance by stabilizing MGMT in glioblastoma.Cell death & disease · 2025Article
- AKT and DUBs: a bidirectional relationship.Cellular & molecular biology letters · 2025Review
- Broad-spectrum ubiquitin-specific protease inhibition as a mechanism for the cytotoxicity of YM155 in cancers.Scientific reports · 2025Article
- USP7 V517F mutation as a mechanism of inhibitor resistance.Nature communications · 2025Article
- Drug resistance mechanisms and treatment strategies mediated by Ubiquitin-Specific Proteases (USPs) in cancers: new directions and therapeutic options.Molecular cancer · 2024Review
- Review
- The disruption of the CCDC6 - PP4 axis induces a BRCAness like phenotype and sensitivity to PARP inhibitors in high-grade serous ovarian carcinoma.Journal of experimental & clinical cancer research : CR · 2022Article
- The emerging landscape of exosomal CircRNAs in solid cancers and hematological malignancies.Biomarker research · 2022Review
- Emerging Proteins in CRPC: Functional Roles and Clinical Implications.Frontiers in oncology · 2022Review
- Highlights in USP7 inhibitors for cancer treatment.Frontiers in chemistry · 2022Review
- RNA interference screens discover proteases as synthetic lethal partners of PI3K inhibition in breast cancer cells.Theranostics · 2022Article
- Response prediction biomarkers and drug combinations of PARP inhibitors in prostate cancer.Acta pharmacologica Sinica · 2021Review
- The tumour suppressor CCDC6 is involved in ROS tolerance and neoplastic transformation by evading ferroptosis.Heliyon · 2021Article
- The Role of PARP Inhibitors in the Treatment of Prostate Cancer: Recent Advances in Clinical Trials.Biomolecules · 2021Review
- Ubiquitin-specific protease 7 as a potential therapeutic target in dogs with hematopoietic malignancies.Journal of veterinary internal medicine · 2021Article
- Deubiquitinase USP7 contributes to the pathogenicity of spinal and bulbar muscular atrophy.The Journal of clinical investigation · 2021Article
- USP7 promotes hepatoblastoma progression through activation of PI3K/AKT signaling pathway.Cancer biomarkers : section A of Disease markers · 2021Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purpose of the studyReduced levels of the tumor suppressor protein CCDC6 sensitize cancer cells to the treatment with PARP-inhibitors. The turnover of CCDC6 protein is regulated by the de-ubiquitinase USP7, which also controls the androgen receptor (AR) stability. Here, we correlated the expression levels of CCDC6 and USP7 proteins in primary prostate cancers (PC). Moreover, we tested the efficacy of the USP7 inhibitors, in combination with PARP-inhibitors as a novel therapeutic option in advanced prostate cancer.Experimental techniques: PC cells were exposed to USP7 inhibitor, P5091, together with cycloheximide, to investigate the turnover of the USP7 substrates, AR and CCDC6. As outcome of the AR downregulation, transcription targets of AR and its variant V7 were examined by qPCR. As a result of CCDC6 degradation, the induction of PARP inhibitors sensitivity was evaluated by analyzing PC cells viability and foci formation. We scored and correlated CCDC6 and USP7 expression levels in a prostate cancer tissue microarray (TMA).
resultsP5091 accelerated the degradation of AR and V7 isoform affecting PSA, UBE2C, CDC20 transcription and PC cells proliferation. Moreover, P5091 accelerated the degradation of CCDC6 sensitizing the cells to PARP-inhibitors, that acted sinergistically with genotoxic agents. The immunohistochemical analysis of both CCDC6 and USP7 proteins exhibited significant correlation for the intensity of staining (p ≤ 0.05).Data interpretation: Thus, CCDC6 and USP7 represent predictive markers for the combined treatment of the USP7-inhibitors and PARP-inhibitors in advanced prostate cancer.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.