ArticleOncotarget2016
Radiosensitization by the investigational NEDD8-activating enzyme inhibitor MLN4924 (pevonedistat) in hormone-resistant prostate cancer cells.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 35 citations in OpenAlex.
- Decoding the ubiquitin network: molecular mechanisms and therapeutic vulnerabilities for precision radio-sensitization in cancer.Molecular cancer · 2025Review
- Protein neddylation and its role in health and diseases.Signal transduction and targeted therapy · 2024Review
- Targeting NEDD8-activating enzyme for cancer therapy: developments, clinical trials, challenges and future research directions.Journal of hematology & oncology · 2023Review
- NEDD8 promotes radioresistance via triggering autophagy formation and serves as a novel prognostic marker in oral squamous cell carcinoma.Cancer cell international · 2023Article
- NEDD8-conjugating enzyme E2s: critical targets for cancer therapy.Cell death discovery · 2023Review
- Targeting cullin neddylation for cancer and fibrotic diseases.Theranostics · 2023Review
- Inhibition of Neddylation Suppresses Osteoclast Differentiation and Function In Vitro and Alleviates Osteoporosis In Vivo.Biomedicines · 2022Article
- Targeting neddylation E2s: a novel therapeutic strategy in cancer.Journal of hematology & oncology · 2021Review
- The Absence of PTEN in Breast Cancer Is a Driver of MLN4924 Resistance.Frontiers in cell and developmental biology · 2021Article
- Neddylation inactivation represses androgen receptor transcription and inhibits growth, survival and invasion of prostate cancer cells.Neoplasia (New York, N.Y.) · 2020Article
- Targeting Cullin-RING E3 Ligases for Radiosensitization: From NEDDylation Inhibition to PROTACs.Frontiers in oncology · 2020Review
- Preclinical studies reveal MLN4924 is a promising new retinoblastoma therapy.Cell death discovery · 2020Article
- Transient inhibition of neddylation at neonatal stage evokes reversible cardiomyopathy and predisposes the heart to isoproterenol-induced heart failure.American journal of physiology. Heart and circulatory physiology · 2019Article
- Inhibition of neddylation modification by MLN4924 sensitizes hepatocellular carcinoma cells to sorafenib.Oncology reports · 2019Article
- Analysis of MLN4924 (pevonedistat) as a potential therapeutic agent in malignant melanoma.Melanoma research · 2018Article
- Protein neddylation and its alterations in human cancers for targeted therapy.Cellular signalling · 2018Review
- Neddylation inhibitor MLN4924 induces GOncology letters · 2018Article
- Chromatin-Bound Cullin-Ring Ligases: Regulatory Roles in DNA Replication and Potential Targeting for Cancer Therapy.Frontiers in molecular biosciences · 2018Review
- Review
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Salvage radiotherapy (SRT) is the first-line treatment for prostate cancer patients with biochemical recurrence following radical prostatectomy, and new specific radiosensitizers are in urgent need to enhance SRT effect. MLN4924 (also known as Pevonedistat), a specific inhibitor of NEDD8-activating enzyme, has recently entered phase I/II clinical trials in several malignancies. By inhibiting cullin neddylation, MLN4924 inactivates Cullin-RING ligases (CRL), which have been validated as an attractive radiosensitizing target. In our study, we demonstrate that MLN4924 can be used as a potent radiosensitizer in hormone-resistant prostate cancer cells. We found that MLN4924 inhibited cullin neddylation and sensitized prostate cancer cells to irradiation (IR). Mechanistically, MLN4924 enhanced IR-induced G2 cell-cycle arrest, by inducing accumulation of WEE1/p21/p27, three well-known CRL substrates. Importantly, siRNA knockdown of WEE1/p21/p27 partially abrogated MLN4924-induced G2 cell-cycle arrest, indicating a causal role of WEE1/p21/p27 in MLN4924-induced radiosensitization. Further mechanistic studies revealed that induction of DNA damage and apoptosis also contributed to MLN4924 radiosensitization in hormone-resistant prostate cancer cells. Our findings lay the foundation for future application of MLN4924 as a potential radiosensitizer in hormone refractory prostate cancer (HRPC).
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Registered trials
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.