ArticleCancer biology & therapy2014
RAD50 targeting impairs DNA damage response and sensitizes human breast cancer cells to cisplatin therapy.
Article in Cancer biology & therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
14 citing papers in PubMed, 28 citations in OpenAlex.
- Identification of a genetic signature enriching for response to ibrutinib in relapsed/refractory follicular lymphoma in the DAWN phase 2 trial.Cancer medicine · 2022Trial
- USP18 Impacts Cisplatin Resistance in Ovarian Cancer Cells by Modulating DNA Repair.International journal of biological sciences · 2026Article
- Targeting DNA damage sensors for cancer therapy.DNA repair · 2025Review
- Targeting DNA damage repair mechanism by using RAD50-silencing siRNA nanoparticles to enhance radiotherapy in triple negative breast cancer.Materials today. Bio · 2024Article
- DNA Repair Mechanisms, Protein Interactions and Therapeutic Targeting of the MRN Complex.Cancers · 2022Review
- Impact of DNA damage response defects in cancer cells on response to immunotherapy and radiotherapy.Journal of medical imaging and radiation oncology · 2022Review
- RAD50 deficiency is a predictor of platinum sensitivity in sporadic epithelial ovarian cancers.Molecular biomedicine · 2020Article
- ASH2L drives proliferation and sensitivity to bleomycin and other genotoxins in Hodgkin's lymphoma and testicular cancer cells.Cell death & disease · 2020Article
- MRE11-RAD50-NBS1 complex alterations and DNA damage response: implications for cancer treatment.Molecular cancer · 2019Review
- ER-α36 mediates cisplatin resistance in breast cancer cells through EGFR/HER-2/ERK signaling pathway.Journal of experimental & clinical cancer research : CR · 2018Article
- Aberrant DNA Double-strand Break Repair Threads in Breast Carcinoma: Orchestrating Genomic Insult Survival.Journal of cancer prevention · 2016Review
- Real-time monitoring of cisplatin cytotoxicity on three-dimensional spheroid tumor cells.Drug design, development and therapy · 2016Article
- Monitoring the effects of doxorubicin on 3D-spheroid tumor cells in real-time.OncoTargets and therapy · 2016Article
- Lentivirus-mediated Knockdown of HDAC1 Uncovers Its Role in Esophageal Cancer Metastasis and Chemosensitivity.Journal of Cancer · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 8 institutions in 8 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In tumor cells the effectiveness of anti-neoplastic agents that cause cell death by induction of DNA damage is influenced by DNA repair activity. RAD50 protein plays key roles in DNA double strand breaks repair (DSBs), which is crucial to safeguard genome integrity and sustain tumor suppression. However, its role as a potential therapeutic target has not been addressed in breast cancer. Our aim in the present study was to analyze the expression of RAD50 protein in breast tumors, and evaluate the effects of RAD50-targeted inhibition on the cytotoxicity exerted by cisplatin and anthracycline and taxane-based therapies in breast cancer cells. Immunohistochemistry assays on tissue microarrays indicate that the strong staining intensity of RAD50 was reduced in 14% of breast carcinomas in comparison with normal tissues. Remarkably, RAD50 silencing by RNA interference significantly enhanced the cytotoxicity of cisplatin. Combinations of cisplatin with doxorubicin and paclitaxel drugs induced synergistic effects in early cell death of RAD50-deficient MCF-7, SKBR3, and T47D breast cancer cells. Furthermore, we found an increase in the number of DSBs, and delayed phosphorylation of histone H2AX after cisplatin treatment in RAD50-silenced cells. These cellular events were associated to a dramatical increase in the frequency of chromosomal aberrations and a decrease of cell number in metaphase. In conclusion, our data showed that RAD50 abrogation impairs DNA damage response and sensitizes breast cancer cells to cisplatin-combined therapies. We propose that the development and use of inhibitors to manipulate RAD50 levels might represent a promising strategy to sensitize breast cancer cells to DNA damaging agents.
Indexed as
Identifiers
What OpenQuestion holds
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.