ArticleCell reports. Medicine2023
Targeting the TCA cycle through cuproptosis confers synthetic lethality on ARID1A-deficient hepatocellular carcinoma.
Article in Cell reports. Medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 55 citations in OpenAlex.
- The role of copper and cuproptosis in digestive system cancers: novel therapeutic strategies and mechanistic insights.Cancer biology & therapy · 2026Review
- Mitochondria-targeted peptide-engineered bimetallic nanozymes enable ferroptosis-sensitized cuproptosis for melanoma therapy.Materials today. Bio · 2026Article
- Metabolism, autophagy, and cell death: The triangular axis in tumor survival and therapeutic resistance.Redox biology · 2026Review
- Elesclomol-mediated cuproptosis overcomes cisplatin resistance by restricting epigenetically activated mitochondrial respiration: Novel therapeutic insights into cisplatin-elesclomol combination therapy.Acta pharmaceutica Sinica. B · 2026Article
- Cuproptosis in hepatocellular carcinoma: bridging copper homeostasis with therapeutic horizons.Molecular biology reports · 2026Review
- The roles of chromatin remodeling and 3D genome organization in cancers: from mechanistic insights to emerging treatment options.Molecular cancer · 2026Review
- Copper homeostasis and cuproptosis: molecular mechanisms and therapeutic opportunities.Molecular biomedicine · 2026Review
- Mitochondrial dynamics imbalance in hepatocellular carcinoma: from molecular mechanisms to new strategies for targeted therapy.Translational cancer research · 2026Review
- Lipid Peroxidation in Cancer Therapy: Molecular Mechanisms Involving Oxidative Stress, Cell Death, and Therapeutic Response.Molecules (Basel, Switzerland) · 2026Review
- Metal-dependent regulated cell death: Molecular architecture and translational frontiers.iMeta · 2026Review
- The SWI/SNF complex in tumor metabolism: Mechanisms and therapeutic implications.The Journal of biological chemistry · 2026Review
- Cuproptosis in inflammation and cancer: molecular mechanisms and therapeutic targets.Molecular cancer · 2026Review
- PRR15 suppresses renal cell carcinoma progression via the NF-κB/FDX1 axis to induce cuproptosis and mitochondrial dysfunction.Oncogene · 2026Article
- Tackling cuproptosis: from metabolic rewiring to therapeutic exploitation in cancer.Cellular & molecular immunology · 2026Review
- PIK-III-Mediated Elevation of Thiamine Re-Sensitises Renal Cell Carcinoma to Cuproptosis via Activating PDHA1.Cell proliferation · 2026Article
- Targeting de novo pyrimidine synthesis confers vulnerability to copper-mediated ATR inactivation in PARP inhibitor-resistant ovarian cancer.Nature communications · 2026Article
- Metallic elements and their molecular roles in gastric cancer: Pathogenic mechanisms and therapeutic implications.World journal of gastrointestinal oncology · 2026Review
- Single-Cell Multiomics Decoding of TCIRG1-Mediated Cuproptosis Circuitry Rewiring Immune-Metabolic Landscape in Ischemic Stroke.Translational stroke research · 2026Article
- Cuproptosis: Biomarkers, Mechanisms and Treatments in Diseases.Molecules (Basel, Switzerland) · 2026Review
- Harnessing Cuproptosis resistance to advance cancer therapeutics.Apoptosis : an international journal on programmed cell death · 2026Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
ARID1A is among the most commonly mutated tumor suppressor genes in hepatocellular carcinoma (HCC). In this study, we conduct a CRISPR-Cas9 synthetic lethality screen using ARID1A-deficient HCC cells to identify approaches to treat HCC patients harboring ARID1A deficiency. This strategy reveals that the survival of these ARID1A-deficient HCC cells is highly dependent on genes related to the tricarboxylic acid (TCA) cycle. Mechanistically, ARID1A loss represses expression of key glycolysis-related gene PKM, shifting cellular glucose metabolism from aerobic glycolysis to dependence on the TCA cycle and oxidative phosphorylation. Cuproptosis is a recently defined form of copper-induced cell death reported to directly target the TCA cycle. Here, we find that ARID1A-deficient HCC cells and xenograft tumors are highly sensitive to copper treatment. Together, these results offer evidence of the synthetic lethality between ARID1A deficiency and mitochondrial respiration impairment, suggesting that copper treatment constitutes a promising therapeutic strategy for selectively targeting ARID1A-deficient HCC.
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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.