ArticleClinical cancer research : an official journal of the American Association for Cancer Research2016
mTOR Inhibitors Suppress Homologous Recombination Repair and Synergize with PARP Inhibitors via Regulating SUV39H1 in BRCA-Proficient Triple-Negative Breast Cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed, 150 citations in OpenAlex.
- Sensitizing Colorectal Cancer to PARP Inhibitors: Biomarkers, Mechanisms, and Combination Strategies.International journal of molecular sciences · 2026Review
- Combination of PARP and KRASNature communications · 2026Article
- Article
- Hexavalent chromium promotes malignant transformation via enhanced translation of SUV39H1.Chemico-biological interactions · 2026Article
- Metformin Sensitizes PTEN-deficient Prostate Cancer to PARP Inhibitors by Rebuilding NADPInternational journal of biological sciences · 2026Article
- PARPs and PARP inhibitors: molecular mechanisms and clinical applications.Molecular biomedicine · 2025Review
- Repression of PRMT activities sensitize homologous recombination-proficient ovarian and breast cancer cells to PARP inhibitor treatment.bioRxiv : the preprint server for biology · 2025Article
- The novel tRNA-derived fragment, tiRNA-Met, inhibits the malignant progression of triple-negative breast cancer by regulating RANBP3L via a targeted interaction with SNRPA.Cellular & molecular biology letters · 2025Article
- Inhibition of the STAT3/Fanconi anemia axis is synthetic lethal with PARP inhibition in breast cancer.Nature communications · 2025Article
- Harnessing transcriptional regulation of alternative end-joining to predict cancer treatment.NAR cancer · 2025Article
- Circulating Tumor DNA Profiling Identifies Actionable Mutations as Prognostic Markers in Advanced Neuroendocrine Tumors.Neuroendocrinology · 2025Article
- Review
- ATM inhibition exploits checkpoint defects and ATM-dependent double strand break repair in TP53-mutant glioblastoma.Nature communications · 2024Article
- BRCA1/2 alterations and reversion mutations in the area of PARP inhibitors in high grade ovarian cancer: state of the art and forthcoming challenges.Frontiers in oncology · 2024Review
- Synergistic Effect of Ubiquitin-Specific Protease 14 and Poly(ADP-Ribose) Glycohydrolase Co-Inhibition in BRCA1-Mutant, Poly(ADP-Ribose) Polymerase Inhibitor-Resistant Triple-Negative Breast Cancer Cells.OncoTargets and therapy · 2024Article
- A review of biological targets and therapeutic approaches in the management of triple-negative breast cancer.Journal of advanced research · 2023Review
- Combination Treatment Strategies to Overcome PARP Inhibitor Resistance.Biomolecules · 2023Review
- PARP inhibitors: enhancing efficacy through rational combinations.British journal of cancer · 2023Review
- SUV39H1 is a prognosis and immune microenvironment-related biomarker in diffuse large B-cell lymphoma.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Article
- Article
14 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
purposeTriple-negative breast cancer (TNBC) is a highly heterogeneous disease and has the worst outcome among all subtypes of breast cancers. Although PARP inhibitors represent a promising treatment in TNBC with BRCA1/BRCA2 mutations, there is great interest in identifying drug combinations that can extend the use of PARP inhibitors to a majority of TNBC patients with wild-type BRCA1/BRCA2 Here we explored whether mTOR inhibitors, through modulating homologous recombination (HR) repair, would provide therapeutic benefit in combination with PARP inhibitors in preclinical models of BRCA-proficient TNBC. EXPERIMENTAL
designWe have studied the effects of mTOR inhibitors on HR repair following DNA double-strand breaks (DSB). We further demonstrated the in vitro and in vivo activities of combined treatment of mTOR inhibitors with PARP inhibitors in BRCA-proficient TNBC. Moreover, microarray analysis and rescue experiments were used to investigate the molecular mechanisms of action.
resultsWe found that mTOR inhibitors significantly suppressed HR repair in two BRCA-proficient TNBC cell lines. mTOR inhibitors and PARP inhibitors in combination exhibited strong synergism against these TNBC cell lines. In TNBC xenografts, we observed enhanced efficacy of everolimus in combination with talazoparib (BMN673) compared with either drug alone. We further identified through microarray analysis and by rescue assays that mTOR inhibitors suppressed HR repair and synergized with PARP inhibitors through regulating the expression of SUV39H1 in BRCA-proficient TNBCs.
conclusionsCollectively, these findings strongly suggest that combining mTOR inhibitors and PARP inhibitors would be an effective therapeutic approach to treat BRCA-proficient TNBC patients.
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