ArticleOncotarget2018
Targeting multidrug-resistant ovarian cancer through estrogen receptor α dependent ATP depletion caused by hyperactivation of the unfolded protein response.
Article in Oncotarget, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 32 citations in OpenAlex.
- Effect of extracellular vesicles on malignant tumours: Mechanisms and clinical findings (Review).Oncology letters · 2026Review
- The Role of Endoplasmic Reticulum Stress and Unfolded Protein Response in Gynecological Cancers: A Narrative Review.Cureus · 2025Review
- A necrosis inducer promotes an immunogenic response and destroys ovarian cancers in mouse xenografts and patient ascites organoids.Cancer letters · 2025Article
- Exploring the mechanism of action of succinic acid in ovarian cancer via single-cell sequencing of the tumor immune microenvironment.Frontiers in oncology · 2025Article
- Targeting Autophagy and the Anticipatory Unfolded Protein Response Leads to Increased Breast Cancer Cell Death.microPublication biology · 2025Article
- Article
- Molecular mechanisms of cisplatin resistance in ovarian cancer.Genes & diseases · 2024Review
- Calcium signals and potential therapy targets in ovarian cancer (Review).International journal of oncology · 2023Review
- A Targeted Thorium-227 Conjugate Demonstrates Efficacy in Preclinical Models of Acquired Drug Resistance and Combination Potential with Chemotherapeutics and Antiangiogenic Therapies.Molecular cancer therapeutics · 2023Article
- Computational approaches to identify a novel binding site of BHPI on estrogen receptor alpha.Steroids · 2022Article
- Activators of the Anticipatory Unfolded Protein Response with Enhanced Selectivity for Estrogen Receptor Positive Breast Cancer.Journal of medicinal chemistry · 2022Article
- Hypoxia, endoplasmic reticulum stress and chemoresistance: dangerous liaisons.Journal of experimental & clinical cancer research : CR · 2021Review
- Cancer stem cells, epithelial-mesenchymal transition, ATP and their roles in drug resistance in cancer.Cancer drug resistance (Alhambra, Calif.) · 2021Article
- An oxindole efflux inhibitor potentiates azoles and impairs virulence in the fungal pathogen Candida auris.Nature communications · 2020Article
- Mechanisms of Taxane ResistanceCancers · 2020Review
- Src couples estrogen receptor to the anticipatory unfolded protein response and regulates cancer cell fate under stress.Biochimica et biophysica acta. Molecular cell research · 2020Article
- Review
- MicroRNA-4290 suppresses PDK1-mediated glycolysis to enhance the sensitivity of gastric cancer cell to cisplatin.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2020Article
- A sensitive and simple targeted proteomics approach to quantify transcription factor and membrane proteins of the unfolded protein response pathway in glioblastoma cells.Scientific reports · 2019Article
- Estrogen-independent Myc overexpression confers endocrine therapy resistance on breast cancer cells expressing ERαY537S and ERαD538G mutations.Cancer letters · 2019Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ovarian cancers often recur and tumors acquire resistance to chemotherapy due to overexpression of the ATP-dependent efflux pump, multidrug resistance protein 1 (MDR1/P-glycoprotein/ABCB1). Nontoxic small molecule inhibitors targeting MDR1 have remained largely elusive. Instead, in a novel application of our recently described estrogen receptor α (ERα) biomodulator, BHPI, we targeted MDR1's substrate, ATP. BHPI depletes intracellular ATP and nearly blocks MDR1-mediated drug efflux in ovarian cancer cells by inducing toxic hyperactivation of the endoplasmic reticulum stress sensor, the unfolded protein response (UPR). BHPI increased sensitivity of MDR1 overexpressing multidrug resistant OVCAR-3 ovarian cancer cells to killing by paclitaxel by >1,000 fold. BHPI also restored doxorubicin sensitivity in OVCAR-3 cells and in MDR1 overexpressing breast cancer cells. In an orthotopic OVCAR-3 xenograft model, paclitaxel was ineffective and the paclitaxel-treated group was uniquely prone to form large secondary tumors in adjacent tissue. BHPI alone strongly reduced tumor growth. Notably, tumors were undetectable in mice treated with BHPI plus paclitaxel. Compared to control ovarian tumors, after the combination therapy, levels of the plasma ovarian cancer biomarker CA125 were at least several hundred folds lower; moreover, CA125 levels progressively declined to undetectable. Targeting MDR1 through UPR-dependent ATP depletion represents a promising therapeutic strategy.
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