ArticleCell death & disease2022
Targeted activation of GPER enhances the efficacy of venetoclax by boosting leukemic pyroptosis and CD8+ T cell immune function in acute myeloid leukemia.
Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 24 citations in OpenAlex.
- Targeting the G-protein-coupled estrogen receptor: a novel therapeutic strategy in cutaneous T-cell lymphoma.Blood neoplasia · 2026Article
- FUBP3 mediates MXI1 stability to silence RRAS and hinder MAPK signaling in acute megakaryoblastic leukemia progression.Cancer immunology, immunotherapy : CII · 2025Article
- Targeting cell death pathways in acute myeloid leukemia: Molecular mechanisms and clinical implications (Review).Oncology reports · 2025Review
- GPER in metabolic homeostasis and disease: molecular mechanisms, nutritional regulation, and therapeutic potential.Journal of translational medicine · 2025Review
- Mitochondrial metabolism and cancer therapeutic innovation.Signal transduction and targeted therapy · 2025Review
- NRF2 maintains redox balance via ME1 and NRF2 inhibitor synergizes with venetoclax in NPM1-mutated acute myeloid leukemia.Cancer & metabolism · 2025Article
- The novel BCL-2/BCL-XL inhibitor APG-1252-mediated cleavage of GSDME enhances the antitumor efficacy of HER2-targeted therapy in HER2-positive gastric cancer.Acta pharmacologica Sinica · 2025Article
- Oxaliplatin induces pyroptosis in hepatoma cells and enhances antitumor immunity against hepatocellular carcinoma.British journal of cancer · 2025Article
- FGFC1 overcomes Ara-C resistance in acute myeloid leukemia by inducing apoptosis and pyroptosis.Frontiers in pharmacology · 2025Article
- Anagrelide and idarubicin combination induces GSDME-mediated pyroptosis as a potential therapy for high-PDE3A acute myeloid leukemia.Leukemia · 2025Article
- Successful remission induction therapy with azacitidine and venetoclax for a treatment-naive elderly patient with ETP/myeloid mixed-phenotype acute leukemia: a case report.Frontiers in oncology · 2025Article
- MAPK Signaling Pathway Plays Different Regulatory Roles in the Effects of Boric Acid on Proliferation, Apoptosis, and Immune Function of Splenic Lymphocytes in Rats.Biological trace element research · 2024Article
- Mitochondrial outer membrane protein MTUS1/ATIP1 exerts antitumor effects through ROS-induced mitochondrial pyroptosis in head and neck squamous cell carcinoma.International journal of biological sciences · 2024Article
- GPER deletion triggers inhibitory effects in triple negative breast cancer (TNBC) cells through the JNK/c-Jun/p53/Noxa transduction pathway.Cell death discovery · 2023Article
- Article
- LNS8801 inhibits Acute Myeloid Leukemia by Inducing the Production of Reactive Oxygen Species and Activating the Endoplasmic Reticulum Stress Pathway.Cancer research communications · 2023Article
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acute myeloid leukemia (AML) is a rapidly progressing and often fatal hematopoietic malignancy. Venetoclax (VEN), a recent FDA-approved BCL-2 selective inhibitor, has high initial response rates in elderly AML patients, but the majority of patients eventually acquire resistance. Multiple studies have demonstrated that the female sex is associated with better outcomes in patients with AML, which are predominantly attributed to estrogen signaling. As a novel membrane estrogen receptor, G protein-coupled estrogen receptor (GPER)-mediated-rapid estrogen effects have attracted considerable attention. However, whether targeting GPER enhances the antileukemic activity of VEN is unknown. In this study, we first demonstrated that GPER expression was dramatically reduced in AML cells owing to promoter hypermethylation. Furthermore, pharmacological activation of GPER by G-1 combined with VEN resulted in synergistic antileukemic activity in vitro and in vivo. Mechanistically, G-1/VEN combination synergistically triggered concurrent mitochondria-related apoptosis and gasdermin E (GSDME)-dependent pyroptosis by activating p38-MAPK/myeloid cell leukemia 1 (MCL-1) axis. Importantly, leukemic pyroptosis heightened CD8+ T cell immune function by releasing interleukin (IL)-1β/18 into the tumor microenvironment. Our study corroborates that GPER activation shows a synergistic antileukemic effect with VEN, making it a promising therapeutic regimen for AML.
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