ArticleNPJ precision oncology2022
Targeting Mre11 overcomes platinum resistance and induces synthetic lethality in XRCC1 deficient epithelial ovarian cancers.
Article in NPJ precision oncology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 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
17 citing papers in PubMed, 21 citations in OpenAlex.
- XYL-1 and Olaparib Synergistically Inhibit the Growth of Pancreatic Cancer by Suppressing the SCD1/BRCA1 Signaling Pathway.Molecules (Basel, Switzerland) · 2026Article
- Clinicopathological and functional evaluation of replication protein A in epithelial ovarian cancers: A target validation study.Translational oncology · 2026Article
- Exploiting synthetic lethality in epithelial ovarian cancer: multi-dimensional approaches beyond DNA damage repair.Molecular cancer · 2026Review
- The inhibition of the MRN complex by Mirin radiosensitizes particularly HPV-negative HNSCC cell lines.Cancer cell international · 2026Article
- Elucidating the dynamic tumor microenvironment through deep transcriptomic analysis and therapeutic implication of MRE11 expression patterns in hepatocellular carcinoma.Cancer cell international · 2025Article
- ZNF451 collaborates with RNF8 to regulate RNF168 localization and amplify ubiquitination signaling to promote DNA damage repair and regulate radiosensitivity.Cell death and differentiation · 2025Article
- DNA repair and the contribution to chemotherapy resistance.Genome medicine · 2025Review
- PRDX1 protects ATM from arsenite-induced proteotoxicity and maintains its stability during DNA damage signaling.Oncotarget · 2025Article
- Structure-specific nucleases in genome dynamics and strategies for targeting cancers.Journal of molecular cell biology · 2024Review
- Prognostic model of lung adenocarcinoma based on immunoprognosis-related genes and related drug prediction.Journal of thoracic disease · 2024Article
- Exploiting the bile acid binding protein as transporter of a Cholic Acid/Mirin bioconjugate for potential applications in liver cancer therapy.Scientific reports · 2024Article
- X-ray cross-complementing family: the bridge linking DNA damage repair and cancer.Journal of translational medicine · 2023Review
- Mapping the MOB proteins' proximity network reveals a unique interaction between human MOB3C and the RNase P complex.The Journal of biological chemistry · 2023Article
- Review
- Selective Killing of BRCA2-Deficient Ovarian Cancer Cells via MRE11 Blockade.International journal of molecular sciences · 2023Article
- DNA Damage Response Alterations in Ovarian Cancer: From Molecular Mechanisms to Therapeutic Opportunities.Cancers · 2023Review
- Evolving DNA repair synthetic lethality targets in cancer.Bioscience reports · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 3 institutions in 3 countries.
Funding
Abstract
Platinum resistance is a clinical challenge in ovarian cancer. Platinating agents induce DNA damage which activate Mre11 nuclease directed DNA damage signalling and response (DDR). Upregulation of DDR may promote chemotherapy resistance. Here we have comprehensively evaluated Mre11 in epithelial ovarian cancers. In clinical cohort that received platinum- based chemotherapy (n = 331), Mre11 protein overexpression was associated with aggressive phenotype and poor progression free survival (PFS) (p = 0.002). In the ovarian cancer genome atlas (TCGA) cohort (n = 498), Mre11 gene amplification was observed in a subset of serous tumours (5%) which correlated highly with Mre11 mRNA levels (p < 0.0001). Altered Mre11 levels was linked with genome wide alterations that can influence platinum sensitivity. At the transcriptomic level (n = 1259), Mre11 overexpression was associated with poor PFS (p = 0.003). ROC analysis showed an area under the curve (AUC) of 0.642 for response to platinum-based chemotherapy. Pre-clinically, Mre11 depletion by gene knock down or blockade by small molecule inhibitor (Mirin) reversed platinum resistance in ovarian cancer cells and in 3D spheroid models. Importantly, Mre11 inhibition was synthetically lethal in platinum sensitive XRCC1 deficient ovarian cancer cells and 3D-spheroids. Selective cytotoxicity was associated with DNA double strand break (DSB) accumulation, S-phase cell cycle arrest and increased apoptosis. We conclude that pharmaceutical development of Mre11 inhibitors is a viable clinical strategy for platinum sensitization and synthetic lethality in ovarian cancer.
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.