ArticleJournal of experimental & clinical cancer research : CR2019
CCDC6 and USP7 expression levels suggest novel treatment options in high-grade urothelial bladder cancer.
Article in Journal of experimental & clinical cancer research : CR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 52 citations in OpenAlex.
- Ubiquitylation-oxaliplatin-related prognosis signature reveals the landscapes of immune responses, cell communication, and therapeutic sensitivity for colorectal cancer.Anti-cancer drugs · 2026Article
- Oncogenic Role and Drug Resistance Effect of CCDC6 in iCCA: Potential Strategies for Targeted Intervention.Journal of cellular and molecular medicine · 2025Article
- Tumor-intrinsic ENO1 inhibition promotes antitumor immune response and facilitates the efficacy of anti-PD-L1 immunotherapy in bladder cancer.Journal of experimental & clinical cancer research : CR · 2025Article
- Usp7 contributes to the tail regeneration of planarians via Islet/Wnt1 axis.Journal of translational medicine · 2025Article
- The KLF16/MYC feedback loop is a therapeutic target in bladder cancer.Journal of experimental & clinical cancer research : CR · 2024Article
- Targeting ubiquitin specific proteases (USPs) in cancer immunotherapy: from basic research to preclinical application.Journal of experimental & clinical cancer research : CR · 2023Review
- ZEB1-mediated biogenesis of circNIPBL sustains the metastasis of bladder cancer via Wnt/β-catenin pathway.Journal of experimental & clinical cancer research : CR · 2023Article
- E3 ubiquitin ligases and deubiquitinases in bladder cancer tumorigenesis and implications for immunotherapies.Frontiers in immunology · 2023Review
- The role of E3 ubiquitin ligases and deubiquitinases in bladder cancer development and immunotherapy.Frontiers in immunology · 2023Review
- 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
- Ubiquitin-specific protease 35 (USP35) mediates cisplatin-induced apoptosis by stabilizing BIRC3 in non-small cell lung cancer.Laboratory investigation; a journal of technical methods and pathology · 2022Article
- RelB upregulates PD-L1 and exacerbates prostate cancer immune evasion.Journal of experimental & clinical cancer research : CR · 2022Article
- Highlights in USP7 inhibitors for cancer treatment.Frontiers in chemistry · 2022Review
- 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
- Targeting WD repeat domain 5 enhances chemosensitivity and inhibits proliferation and programmed death-ligand 1 expression in bladder cancer.Journal of experimental & clinical cancer research : CR · 2021Article
- Toll-Like Receptor 7 Mediates Inflammation Resolution and Inhibition of Angiogenesis in Non-Small Cell Lung Cancer.Cancers · 2021Article
- USP16 regulates castration-resistant prostate cancer cell proliferation by deubiquitinating and stablizing c-Myc.Journal of experimental & clinical cancer research : CR · 2021Article
- Expression of Ubiquitin-specific protease 7 in oral squamous cell carcinoma promotes tumor cell proliferation and invasion.Genetics and molecular biology · 2021Article
- Coiled-coil domain-containing 68 promotes non-small cell lung cancer cell proliferationOncology letters · 2020Article
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10 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundThe muscle invasive form of urothelial bladder cancer (UBC) is a deadly disease. Currently, the therapeutic approach of UBC is mostly based on surgery and standard chemotherapy. Biomarkers to establish appropriate drugs usage are missing. Deficiency of the tumor suppressor CCDC6 determines PARP-inhibitor sensitivity. The CCDC6 levels are modulated by the deubiquitinase USP7. In this work we scored CCDC6 and USP7 expression levels in primary UBC and we evaluated the expression levels of CCDC6 in correlation with the effects of the PARP-inhibitors combined with the USP7 inhibitor, P5091, in vitro. Since PARP-inhibitors could be enhanced by conventional chemotherapy or DNA damage inducers, we tested the new agent RRx-001, able to induce DNA damage, to prove the benefit of combined treatments in bladder cancer cells.
methodsThe J82, T24, 5637 and KU-19-19 bladder cancer cells were exposed to USP7 inhibitor P5091 in presence of cycloheximide to analyse the CCDC6 stability. Upon the CCDC6 degradation induced by P5091, the cells sensitivity to PARP-inhibitor was evaluated by cell viability assays. The ability of the DNA damage inducer RRx-001 to modulate CCDC6 protein levels and H2AX phosphorylation was detected at immunoblot. The combination of USP7 inhibitor plus RRx-001 enhanced the PARP-inhibitor sensitivity, as evaluated by cell viability assays. The results of the scores and correlation of CCDC6 and USP7 expression levels obtained by UBC primary biopsies staining were used to cluster patients by a K-mean cluster analysis.
resultsP5091 determining CCDC6 degradation promoted bladder cancer cells sensitivity to PARP-inhibitor drugs. RRx-001, by inducing DNA damage, enhanced the effects of the combined treatment. The immunohistochemical staining of both CCDC6 and USP7 proteins allowed to cluster the high grade (G3) UBC patients, on the basis of CCDC6 expression levels.
conclusionsIn high grade UBC the identification of two clusters of patients based on CCDC6 and USP7 expession can possibly indicate the use of PARP-inhibitor drugs, in combination with USP7 inhibitor in addition to the DNA damage inducer RRx-001, that also acts as an immunomodulatory agent, offering novel therapeutic strategy for personalized medicine in bladder cancer patients.
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