ArticleCancer cell2023
Targeting the mevalonate pathway suppresses ARID1A-inactivated cancers by promoting pyroptosis.
Article in Cancer cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 79 citations in OpenAlex.
- The dual immune landscape of homologous recombination-deficient tumors: mechanisms and therapeutic implications.Cancer metastasis reviews · 2026Review
- ARID1A regulates colorectal cancer metastasis through the AKT/mTOR/p70S6K pathway.Translational oncology · 2026Article
- The roles of chromatin remodeling and 3D genome organization in cancers: from mechanistic insights to emerging treatment options.Molecular cancer · 2026Review
- Emerging roles of the metabolic regulator 3-hydroxy-3-methylglutaryl coenzyme-CoA reductase in human cancers: From biology to therapeutics.Genes & diseases · 2026Review
- Knockdown of ARID1A Protects H9c2 Cells Against Hypoxia/Reoxygenation (H/R)-Induced Injury by Targeting SOX9.Korean circulation journal · 2026Article
- Repurposing atorvastatin for uterine leiomyosarcoma: mevalonate pathway inhibition yields preclinical antitumor efficacy.Acta pharmacologica Sinica · 2026Article
- ARID1A loss drives gastric signet ring cell carcinoma by regulating mucin production and secretion.Nature communications · 2026Article
- Comprehensive molecular characterization identifies therapeutic vulnerabilities in ovarian clear cell carcinoma.Genome medicine · 2026Article
- Lipophilic Statins Deplete GPX4 to Promote Ferroptosis and Sensitize Cancer Cells to Immune Checkpoint Blockade.Molecular cancer therapeutics · 2026Article
- Targeting methionine-induced pyroptosis enhances anti-tumor immunity.Science China. Life sciences · 2026Article
- Statins targeting mevalonate-geranylgeranyl diphosphate pathway inhibit proliferation in NK/T lymphoma by promoting pyroptosis.Translational oncology · 2026Article
- Lipid metabolism reprogramming shapes the immune landscape in the tumor microenvironment.Cellular & molecular immunology · 2026Review
- Ferroptosis as a therapeutic vulnerability in ARID1A-deficient bladder cancer.Communications biology · 2026Article
- ARID1A deficiency-driven reprogramming of polyamine metabolism promotes endometrial cancer malignancy and immune escape.Cell death & disease · 2026Article
- pH-responsive ZIF-8@quercetin nanoparticles induce pyroptosis for targeted gastric cancer therapy.Materials today. Bio · 2026Article
- Inhibition of PRMT5 triggers synthetic lethality in ARID1A-deficient endometrial cancer by promoting aberrant R-loop accumulation.Molecular cancer · 2026Article
- The molecular mechanisms of pyroptosis and its implications in tumor immunotherapy.Molecular cancer · 2026Review
- Exploring Lipid Metabolic Reprogramming: Mechanistic Insights and Implications for Tumor Radiotherapy.International journal of biological sciences · 2026Review
- ZCCHC4 Orchestrates Hepatocellular Carcinoma Metastasis by Regulating Lipid biosynthesis and TMEM97/LCN2/Twist1 Pathway.International journal of biological sciences · 2026Article
- Regulated cell death in ovarian cancer: molecular mechanisms and therapeutic targets.Frontiers in cell and developmental biology · 2026Review
2 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
21 authors at 3 institutions in 2 countries.
Funding
Abstract
ARID1A, encoding a subunit of the SWI/SNF complex, is mutated in ∼50% of clear cell ovarian carcinoma (OCCC) cases. Here we show that inhibition of the mevalonate pathway synergizes with immune checkpoint blockade (ICB) by driving inflammasome-regulated immunomodulating pyroptosis in ARID1A-inactivated OCCCs. SWI/SNF inactivation downregulates the rate-limiting enzymes in the mevalonate pathway such as HMGCR and HMGCS1, which creates a dependence on the residual activity of the pathway in ARID1A-inactivated cells. Inhibitors of the mevalonate pathway such as simvastatin suppresses the growth of ARID1A mutant, but not wild-type, OCCCs. In addition, simvastatin synergizes with anti-PD-L1 antibody in a genetic OCCC mouse model driven by conditional Arid1a inactivation and in a humanized immunocompetent ARID1A mutant patient-derived OCCC mouse model. Our data indicate that inhibition of the mevalonate pathway simultaneously suppresses tumor cell growth and boosts antitumor immunity by promoting pyroptosis, which synergizes with ICB in suppressing ARID1A-mutated cancers.
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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.