ArticleNature cancer2021
LXRα activation and Raf inhibition trigger lethal lipotoxicity in liver cancer.
Article in Nature cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 55 citations in OpenAlex.
- The pivotal role of SCD1 in digestive cancers: Bridging lipid metabolic reprogramming and programmed cell death (Review).International journal of oncology · 2026Review
- CEBPG-Mediated Palmitic Acid Adaptation of Cancer-Associated Fibroblasts Drives Metastasis of Oral Squamous Cell Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The versatile interplay between steatotic liver disease and liver cancer.Nature reviews. Cancer · 2026Review
- Role of liver X receptors in the pathogenesis and treatment of chronic liver disease (Review).Molecular medicine reports · 2026Review
- Large adipocytes increase vesicle-mediated lipid release and promote breast cancer malignancy.Cell reports · 2026Article
- Revisiting cholesterol metabolism in hepatocellular carcinoma: a hidden driver of systemic therapy response.ESMO gastrointestinal oncology · 2026Review
- Review
- Metabolic Reprogramming-Targeted Therapeutic Strategies in Primary Liver Cancer: A Bibliometric and Visualized Analysis.Journal of hepatocellular carcinoma · 2026Article
- Cholesterol metabolic rewiring shapes immune remodeling across hepatocarcinogenesis.Frontiers in immunology · 2026Review
- Atorvastatin negatively regulates MAPK pathway in vitro to inhibit proliferation, migration, and invasion of hepatocellular carcinoma cells.Scientific reports · 2025Article
- Lipid metabolism in cancer cells: Its role in hepatocellular carcinoma progression and therapeutic resistance.Hepatology communications · 2025Review
- Large adipocytes alter mode of lipid release and promote breast cancer malignancy.bioRxiv : the preprint server for biology · 2025Article
- Uncovering α-Selectivity for Liver X Receptor Agonists for Lipotoxic Cancer Therapies.Journal of medicinal chemistry · 2025Article
- Targeting aldolase A in hepatocellular carcinoma leads to imbalanced glycolysis and energy stress due to uncontrolled FBP accumulation.Nature metabolism · 2025Article
- First-in-class ultralong-target-residence-time p38α inhibitors as a mitosis-targeted therapy for colorectal cancer.Nature cancer · 2025Article
- Nuclear receptor-driven immunometabolic crosstalk: immune-centric pharmacology targeting the inflamed nexus.Frontiers in cell and developmental biology · 2025Review
- The Role of MAPK12 in Prognosis of Patients With Liver Cancer and Effects on Stemness Characteristics.Stem cells international · 2025Article
- SPP1+ tumor-associated macrophages define a high-risk subgroup and inform personalized therapy in hepatocellular carcinoma.Frontiers in oncology · 2025Article
- The comprehensive SARS-CoV-2 'hijackome' knowledge base.Cell discovery · 2024Article
- Fatty Acid Synthase (FASN) Inhibitors Suppress Metformin-Induced Fat Accumulation and Apoptosis in H4IIE Hepatocellular Carcinoma Cells.Development & reproduction · 2024Article
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Authors and funding
26 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The success of molecular therapies targeting specific metabolic pathways in cancer is often limited by the plasticity and adaptability of metabolic networks. Here we show that pharmacologically induced lipotoxicity represents a promising therapeutic strategy for the treatment of hepatocellular carcinoma (HCC). LXRα-induced liponeogenesis and Raf-1 inhibition are synthetic lethal in HCC owing to a toxic accumulation of saturated fatty acids. Raf-1 was found to bind and activate SCD1, and conformation-changing DFG-out Raf inhibitors could disrupt this interaction, thereby blocking fatty acid desaturation and inducing lethal lipotoxicity. Studies in genetically engineered and nonalcoholic steatohepatitis-induced HCC mouse models and xenograft models of human HCC revealed that therapies comprising LXR agonists and Raf inhibitors were well tolerated and capable of overcoming therapy resistance in HCC. Conceptually, our study suggests pharmacologically induced lipotoxicity as a new mode for metabolic targeting of liver cancer.
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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.