ArticleNature communications2025
Precision targeting of β-catenin induces tumor reprogramming and immunity in hepatocellular cancers.
Article in Nature communications, 2025. 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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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.
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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
24 citing papers in PubMed.
- Alcohol reshapes liver zonal plasticity and immune-metabolic reprogramming in metabolic-syndrome associated hepatocellular carcinoma.Nature communications · 2026Article
- Molecular subtyping of adrenocortical carcinoma reveals distinct subtypes with prognostic and therapeutic implications.Endocrine-related cancer · 2026Article
- Wnt/β-catenin signaling in hepatocellular carcinoma: a key player in resistance to targeted and immunotherapies.Carcinogenesis · 2026Review
- Cancer Heterogeneity and Cancer Cell Plasticity: Molecular Mechanisms and Precision Therapy.MedComm · 2026Review
- Advances in oncolytic viruses immunotherapy of hepatocellular carcinoma.Discover oncology · 2026Review
- Article
- From Theory to Practice: Which Biomarkers Are Ready for Predicting Response in Advanced HCC?Liver international : official journal of the International Association for the Study of the Liver · 2026Review
- Nucleic Acid Therapeutics for "Undruggable" Cancer Targets: Mechanisms, Challenges, and Prospects.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- WNT-β-catenin signalling in hepatocellular carcinoma: from bench to clinical trials.Nature reviews. Gastroenterology & hepatology · 2026Review
- Translating Fibrosis to Malignancy: Biomarkers and Therapeutic Opportunities in Liver Fibrosis and Hepatocellular Carcinoma.Medical sciences (Basel, Switzerland) · 2026Review
- Advances in nano-delivery systems for overcoming the challenges of applying siRNA drugs in tumor therapy.Asian journal of pharmaceutical sciences · 2026Review
- Tumor Cells as Architects of Immune Refractoriness: Dismantling Intrinsic Programs of Tumor Cells for Clinical Translation.Immune network · 2026Review
- Article
- Impaired nitrogenous waste clearance promotes hepatocellular carcinoma.Science advances · 2026Article
- Functional Interpretation of Recurrent Genetic Variants in Hepatocellular Carcinoma: Molecular Consequences and Clinical Relevance.Human mutation · 2026Review
- Zonation, Zonation, Zonation: The Real Estate of the Liver.Annual review of pathology · 2026Review
- Preclinical exploration and current clinical applications of immunotherapeutic strategies for hepatocellular carcinoma.Frontiers in immunology · 2026Review
- A novel auto-fluorescent porphyrin-lipid nanoparticle strategy for CTNNB1 gene silencing in hepatocellular carcinoma.Frontiers in oncology · 2026Article
- Navigating second-line therapy after immunotherapy in advanced HCC☆.JHEP reports : innovation in hepatology · 2026Review
- Organoid: a promising solution to current challenges in cancer immunotherapy.npj biomedical innovations · 2025Review
Corrections and comments
- Update of
Authors and funding
35 authors.
Funding
Abstract
First-line immune checkpoint inhibitor (ICI) combinations show responses in subsets of hepatocellular carcinoma (HCC) patients. Nearly half of HCCs are Wnt-active with mutations in CTNNB1 (encoding for β-catenin), AXIN1/2, or APC, and demonstrate heterogeneous and limited benefit to ICI due to an immune excluded tumor microenvironment. We show significant tumor responses in multiple β-catenin-mutated immunocompetent HCC models to a novel siRNA encapsulated in lipid nanoparticle targeting CTNNB1 (LNP-CTNNB1). Both single-cell and spatial transcriptomics reveal cellular and zonal reprogramming, along with activation of immune regulatory transcription factors IRF2 and POU2F1, re-engaged type I/II interferon signaling, and alterations in both innate and adaptive immunity upon β-catenin suppression with LNP-CTNNB1 at early- and advanced-stage disease. Moreover, ICI enhances response to LNP-CTNNB1 in advanced-stage disease by preventing T cell exhaustion and through formation of lymphoid aggregates (LA). In fact, expression of an LA-like gene signature prognosticates survival for patients receiving atezolizumab plus bevacizumab in the IMbrave150 phase III trial and inversely correlates with CTNNB1-mutatational status in this patient cohort. In conclusion, LNP-CTNNB1 is efficacious as monotherapy and in combination with ICI in CTNNB1-mutated HCCs through impacting tumor cell-intrinsic signaling and remodeling global immune surveillance, providing rationale for clinical investigations.
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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.