ArticleCell death & disease2018
Intrinsic apoptotic pathway activation increases response to anti-estrogens in luminal breast cancers.
Article in Cell death & disease, 2018. 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
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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.
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Who cites it
17 citing papers in PubMed, 25 citations in OpenAlex.
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- Synergistic combinatorial anticancer potential of Tamoxifen with Naringin and Diosmetin in MCF-7 breast cancer cells and their liposomal delivery.Scientific reports · 2026Article
- Article
- Emerging opportunities to treat drug-resistant breast cancer: Discovery of novel small-molecule inhibitors against different targets.Frontiers in pharmacology · 2025Review
- Improving Tamoxifen Performance in Inducing Apoptosis and Hepatoprotection by Loading on a Dual Nanomagnetic Targeting System.Anti-cancer agents in medicinal chemistry · 2024Article
- SERPINA3-ANKRD11-HDAC3 pathway induced aromatase inhibitor resistance in breast cancer can be reversed by HDAC3 inhibition.Communications biology · 2023Article
- Estrogen-dependent activation of NCOA3 couples with p300 and NF-κB to mediate antiapoptotic genes in ER-positive breast cancer cells.Discover oncology · 2023Article
- Liver Metastatic Breast Cancer: Epidemiology, Dietary Interventions, and Related Metabolism.Nutrients · 2022Review
- The role of folic acid in inducing of apoptosis by zinc(II) complex in ovary and cervix cancer cells.Molecular diversity · 2022Article
- Transcriptome profiling and proteomic validation reveals targets of the androgen receptor signaling in the BT-474 breast cancer cell line.Clinical proteomics · 2022Article
- Regulation of Bcl-2 Family Proteins in Estrogen Receptor-Positive Breast Cancer and Their Implications in Endocrine Therapy.Cancers · 2022Review
- Diallyl Disulfide: A Bioactive Garlic Compound with Anticancer Potential.Frontiers in pharmacology · 2022Review
- A small-molecule activator of the unfolded protein response eradicates human breast tumors in mice.Science translational medicine · 2021Article
- BH3 mimetics selectively eliminate chemotherapy-induced senescent cells and improve response in TP53 wild-type breast cancer.Cell death and differentiation · 2020Article
- Therapeutic inhibition of Mcl-1 blocks cell survival in estrogen receptor-positive breast cancers.Oncotarget · 2019Article
- In vitro and in vivo effects of traditional Chinese medicine formula T33 in human breast cancer cells.BMC complementary and alternative medicine · 2019Article
- MicroRNA-645 targets urokinase plasminogen activator and decreases the invasive growth of MDA-MB-231 triple-negative breast cancer cells.OncoTargets and therapy · 2018Article
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 4 institutions in 1 country.
Funding
Abstract
Estrogen receptor-α positive (ERα+) breast cancer accounts for approximately 70-80% of the nearly 25,0000 new cases of breast cancer diagnosed in the US each year. Endocrine-targeted therapies (those that block ERα activity) serve as the first line of treatment in most cases. Despite the proven benefit of endocrine therapies, however, ERα+ breast tumors can develop resistance to endocrine therapy, causing disease progression or relapse, particularly in the metastatic setting. Anti-apoptotic Bcl-2 family proteins enhance breast tumor cell survival, often promoting resistance to targeted therapies, including endocrine therapies. Herein, we investigated whether blockade of anti-apoptotic Bcl-2 family proteins could sensitize luminal breast cancers to anti-estrogen treatment. We used long-term estrogen deprivation (LTED) of human ERα+ breast cancer cell lines, an established model of sustained treatment with and acquired resistance to aromatase inhibitors (AIs), in combination with Bcl-2/Bcl-xL inhibition (ABT-263), finding that ABT-263 induced only limited tumor cell killing in LTED-selected cells in culture and in vivo. Interestingly, expression and activity of the Bcl-2-related factor Mcl-1 was increased in LTED cells. Genetic Mcl-1 ablation induced apoptosis in LTED-selected cells, and potently increased their sensitivity to ABT-263. Increased expression and activity of Mcl-1 was similarly seen in clinical breast tumor specimens treated with AI + the selective estrogen receptor downregulator fulvestrant. Delivery of Mcl-1 siRNA loaded into polymeric nanoparticles (MCL1 si-NPs) decreased Mcl-1 expression in LTED-selected and fulvestrant-treated cells, increasing tumor cell death and blocking tumor cell growth. These findings suggest that Mcl-1 upregulation in response to anti-estrogen treatment enhances tumor cell survival, decreasing response to therapeutic treatments. Therefore, strategies blocking Mcl-1 expression or activity used in combination with endocrine therapies would enhance tumor cell death.
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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.