ArticleAmerican journal of cancer research2019
Metformin reverses PARP inhibitors-induced epithelial-mesenchymal transition and PD-L1 upregulation in triple-negative breast cancer.
Article in American journal of cancer research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
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Who cites it
32 citing papers in PubMed, 39 citations in OpenAlex.
- Metformin and its derivatives in breast cancer: from glycaemic control to tumor-intrinsic pathways.Breast cancer research : BCR · 2025Review
- Article
- Therapeutic Potential of Metal-Based and PARP Inhibitor Chemotherapy forInternational journal of molecular sciences · 2025Review
- Mechanisms of Resistance to PARPi in Pancreatic Ductal Adenocarcinoma.Journal of cellular and molecular medicine · 2025Article
- Enhanced integrated therapy for breast cancer employing Honokiol-loaded mesoporous polydopamine nanoparticles in conjunction with photothermal effects and low-dose metformin.APL bioengineering · 2025Article
- Despicable role of epithelial-mesenchymal transition in breast cancer metastasis: ExhibitingCancer pathogenesis and therapy · 2025Review
- Niraparib enhances antitumor immunity and contributes to the efficacy of PD-L1 blockade in cervical cancer.Journal of cancer research and clinical oncology · 2024Article
- The Metformin Immunoregulatory Actions in Tumor Suppression and Normal Tissues Protection.Current medicinal chemistry · 2024Review
- Metformin may improve the outcome of patients with colorectal cancer and type 2 diabetes mellitus partly through effects on neutrophil extracellular traps.BJC reports · 2023Article
- Updates on Triple-Negative Breast Cancer in Type 2 Diabetes Mellitus Patients: From Risk Factors to Diagnosis, Biomarkers and Therapy.Diagnostics (Basel, Switzerland) · 2023Review
- Mechanisms of PARP-Inhibitor-Resistance in BRCA-Mutated Breast Cancer and New Therapeutic Approaches.Cancers · 2023Review
- Metformin improves cancer immunotherapy by directly rescuing tumor-infiltrating CD8 T lymphocytes from hypoxia-induced immunosuppression.Journal for immunotherapy of cancer · 2023Article
- Oligo-Fucoidan supplementation enhances the effect of Olaparib on preventing metastasis and recurrence of triple-negative breast cancer in mice.Journal of biomedical science · 2022Article
- Targeting of the tumor immune microenvironment by metformin.Journal of cell communication and signaling · 2022Review
- Functional regulations between genetic alteration-driven genes and drug target genes acting as prognostic biomarkers in breast cancer.Scientific reports · 2022Article
- Metformin combined with local irradiation provokes abscopal effects in a murine rectal cancer model.Scientific reports · 2022Article
- Shedding light on triple-negative breast cancer with Trop2-targeted antibody-drug conjugates.American journal of cancer research · 2022Review
- Updates in combined approaches of radiotherapy and immune checkpoint inhibitors for the treatment of breast cancer.Frontiers in oncology · 2022Review
- Exploiting induced vulnerability to overcome PARPi resistance and clonal heterogeneity in BRCA mutant triple-negative inflammatory breast cancer.American journal of cancer research · 2022Article
- Metformin reduces PD-L1 on tumor cells and enhances the anti-tumor immune response generated by vaccine immunotherapy.Journal for immunotherapy of cancer · 2021Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Poly (ADP-ribose) polymerase (PARP) inhibitors have emerged as promising targeted therapies for BRCA-mutated cancers by blocking repair of DNA double-strand breaks. However, resistance to PARP inhibitors (PARPi) has been described in some patients lowering the overall response rates. To investigate the underlying mechanisms of PARPi resistance, we developed the adaptive resistant clones in triple-negative breast cancer cell lines. We identified epithelial-mesenchymal transition (EMT) and upregulation of programmed death-ligand 1 (PD-L1) in resistant cells and further demonstrated the important role of Akt S473 phosphorylation in PARPi resistance. In addition, PARPi mediated EMT is independent of PD-L1 upregulation. Blocking the p-Akt S473 axis by metformin reversed EMT and PD-L1 expression which sensitized PARPi-resistant cells to cytotoxic T cells. Thus, a combination of metformin and PARP inhibitors may be a promising therapeutic strategy to increase the efficacy of PARP inhibitors and tumor sensitivity to immunotherapy.
Indexed as
Identifiers
31106005PMC6511636W2995607093What 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.