ArticleOncotarget2018
Inhibition of mTOR downregulates expression of DNA repair proteins and is highly efficient against BRCA2-mutated breast cancer in combination to PARP inhibition.
Article in Oncotarget, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 21 citations in OpenAlex.
- Ultrasound-Assisted Synthesis and Biological Profiling of 1,3,5-Triazine Derivatives with Antiproliferative Activity in Triple-Negative Breast Cancer.Current issues in molecular biology · 2026Article
- FOXD3 promotes homologous recombination repair and genomic stability by facilitating MRE11-mediated DNA end resection.Acta biochimica et biophysica Sinica · 2025Article
- Introduction of AGPAT3 gene as a regulator of cisplatin resistance in A2780 ovarian endometrioid carcinoma cell line.PloS one · 2025Article
- Mechanisms driving fasting-induced protection from genotoxic injury in the small intestine.American journal of physiology. Gastrointestinal and liver physiology · 2024Article
- Intratumoral drug-releasing microdevices allow in situ high-throughput pharmaco phenotyping in patients with gliomas.Science translational medicine · 2023Article
- Unravelling homologous recombination repair deficiency and therapeutic opportunities in soft tissue and bone sarcoma.EMBO molecular medicine · 2023Article
- Combined PARP inhibitors and small molecular inhibitors in solid tumor treatment (Review).International journal of oncology · 2023Review
- Rational Combinations of PARP Inhibitors with HRD-Inducing Molecularly Targeted Agents.Cancer treatment and research · 2023Review
- High-throughput screen to identify compounds that prevent or target telomere loss in human cancer cells.NAR cancer · 2022Article
- Preclinical Studies on the Effect of Rucaparib in Ovarian Cancer: Impact of BRCA2 Status.Cells · 2021Article
- Poly (ADP-ribose) Polymerase Inhibition in Patients with Breast Cancer and BRCA 1 and 2 Mutations.Drugs · 2020Review
- MRE11-RAD50-NBS1 complex alterations and DNA damage response: implications for cancer treatment.Molecular cancer · 2019Review
- Transcriptome Sequencing Investigated the Tumor-Related Factors Changes AfterFrontiers in microbiology · 2019Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Breast cancer is a complex disease in which each patient could present several genetic alterations that are therapeutically relevant in cancers. Here we explored the therapeutic benefit of combining PARP and mTOR inhibitors in a context of DNA repair deficiency and PI3K pathway activation. The combination of everolimus and olaparib was tested in BRCA2-mutated patient-derived xenografts (PDX) carrying alterations in the PI3K/AKT/mTOR pathway. An RPPA analysis of different signalling pathways was performed in untreated and treated xenografts. Everolimus and olaparib showed marked anti-tumor activities in the monotherapy setting and high efficacy when given in combination with 100% of mice showing tumor regressions. The fraction of P-H2AX positive cells was increased in both monotherapy arms and strongly increased in the combination setting. Everolimus given as monotherapy resulted in downregulation of different proteins involved in DNA damage repair, including FANCD2, RAD50 and SUV39H1. In the combination setting, expression of these proteins was almost completely abolished, suggesting convergence of PARP and mTOR in downregulation of DNA damage repair components. In conclusion, our results suggest that combining mTOR and DNA repair inhibition could be a successful strategy to treat a subset of breast cancer with BRCA2 mutation and alterations in the PI3K/AKT/mTOR pathway.
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