ArticleCancers2020
Dual PI3K/mTOR Inhibitor NVP-BEZ235 Enhances Radiosensitivity of Head and Neck Squamous Cell Carcinoma (HNSCC) Cell Lines Due to Suppressed Double-Strand Break (DSB) Repair by Non-Homologous End Joining.
Article in Cancers, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
28 citing papers in PubMed, 39 citations in OpenAlex.
- Phytochemicals and their Nanoformulations for Overcoming Drug Resistance in Head and Neck Squamous Cell Carcinoma.Pharmaceutical research · 2025Review
- SCGB1A1 as a novel biomarker and promising therapeutic target for the management of HNSCC.Oncology letters · 2024Article
- Review
- Non-Homologous End-Joining Pathway Genotypes Significantly Associated with Nasopharyngeal Carcinoma Susceptibility.Biomedicines · 2023Article
- PI3K/AKT/mTOR Signaling Pathway in HPV-Driven Head and Neck Carcinogenesis: Therapeutic Implications.Biology · 2023Review
- DNA Double-Strand Break-Related Competitive Endogenous RNA Network of Noncoding RNA in Bovine Cumulus Cells.Genes · 2023Article
- Targeting K-Ras-mediated DNA damage response in radiation oncology: Current status, challenges and future perspectives.Clinical and translational radiation oncology · 2023Review
- Article
- ZSTK474 Sensitizes Glioblastoma to Temozolomide by Blocking Homologous Recombination Repair.BioMed research international · 2022Article
- IL1 Pathway in HPV-Negative HNSCC Cells Is an Indicator of Radioresistance After Photon and Carbon Ion Irradiation Without Functional Involvement.Frontiers in oncology · 2022Article
- The Fibrotic Effects of TMAO on Human Renal Fibroblasts Is Mediated by NLRP3, Caspase-1 and the PERK/Akt/mTOR Pathway.International journal of molecular sciences · 2021Article
- Diosmetin Induces Modulation of Igf-1 and Il-6 Levels to Alter Rictor-Akt-PKCα Cascade in Inhibition of Prostate Cancer.Journal of clinical medicine · 2021Article
- Biology of the Radio- and Chemo-Responsiveness in HPV Malignancies.Seminars in radiation oncology · 2021Review
- The Pathogenic Role of PI3K/AKT Pathway in Cancer Onset and Drug Resistance: An Updated Review.Cancers · 2021Review
- FOXM1 Promotes Head and Neck Squamous Cell CarcinomaFrontiers in oncology · 2021Article
- Dual Inhibition of PARP and the Intra-S/G2 Cell Cycle Checkpoints Results in Highly Effective Radiosensitization of HPV-Positive HNSCC Cells.Frontiers in oncology · 2021Article
- High Expression of Cancer-IgG Is Associated With Poor Prognosis and RadioresistanceFrontiers in oncology · 2021Article
- Activation of PI3K/AKT/mTOR Pathway Causes Drug Resistance in Breast Cancer.Frontiers in pharmacology · 2021Review
- HS-173, a selective PI3K inhibitor, induces cell death in head and neck squamous cell carcinoma cell lines.Wiener klinische Wochenschrift · 2021Article
- Exploiting DNA repair pathways for tumor sensitization, mitigation of resistance, and normal tissue protection in radiotherapy.Cancer drug resistance (Alhambra, Calif.) · 2021Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
The PI3K/Akt/mTOR pathway is frequently altered in human papillomavirus (HPV)-positive and negative squamous cell carcinoma of the head and neck (HNSCC) and overstimulation is associated with poor prognosis. PI3K drives Akt activation and constitutive signaling acts pro-proliferative, supports cell survival, DNA repair, and contributes to radioresistance. Since the small molecule NVP-BEZ235 (BEZ235) is a potent dual inhibitor of this pathway, we were interested whether BEZ235 could be an efficient radiosensitizer. The 50 nM BEZ235 was found to abrogate endogenous and irradiation-induced phosphorylation of Akt (Ser473). The anti-proliferative capacity of the drug resulted in an increase in G1-phase cells. Repair of radiation-induced DNA double-strand breaks (DSBs) was strongly suppressed. Reduction in DSB repair was only apparent in G1- but not in G2-phase cells, suggesting that BEZ235 primarily affects non-homologous end joining. This finding was confirmed using a DSB repair reporter gene assay and could be attributed to an impaired phosphorylation of DNA-PKcs (S2056). Cellular radiosensitivity increased strongly after BEZ235 addition in all HNSCC cell lines used, especially when irradiated in the G0 or G1 phase. Our data indicate that targeting the PI3K/Akt/mTOR pathway by BEZ235 with concurrent radiotherapy may be considered an effective strategy for the treatment of HNSCC, regardless of the HPV and Akt status.
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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.