ArticleCancer cell2016
An LXR-Cholesterol Axis Creates a Metabolic Co-Dependency for Brain Cancers.
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Article in Cancer cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 214 papers, 2 of them syntheses that pooled it.
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214citing papers in PubMed, 2 pooled it
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214 citing papers in PubMed, 2 syntheses or guidelines pooled it, 324 citations in OpenAlex.
- Recognizing the psychological impact of a glioma diagnosis on mental and behavioral health: a systematic review of what neurosurgeons need to know.Journal of neurosurgery · 2023Pooled it
- Expression of SREBP2 and cholesterol metabolism related genes in TCGA glioma cohorts.Medicine · 2020Pooled it
- Proteomic profiling of cephalic vein reveals potential biomarkers for arteriovenous fistula neointimal hyperplasia in ESRD patients.Renal failure · 2026Article
- Low-Density Lipoprotein Receptor-Targeted Biomimetic Nanoplatform Suppresses Glioblastoma Stemness and Remodels Antitumor Immunity via Dual Metabolic Disruption.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- DHODH is the key target of the KDM4 inhibitor QC6352 in glioblastoma stem cells.Nature chemical biology · 2026Article
- SQOR regulates HResearch square · 2026Article
- Artificial intelligence-guided discovery of fungal ergosterol derivatives as selective LXRβ agonists targeting the cholesterol dependency of glioblastoma.Molecular diversity · 2026Article
- The interplay between lipid metabolism, cancer progression and anti-cancer immunity.Experimental & molecular medicine · 2026Review
- Thr3/Ser90 phosphorylation-stabilized S100A8 regulates cholesterol metabolism in glioblastoma stem cells.Oncogene · 2026Article
- BRI3 Orchestrates Lipid Metabolism and Autophagy in Glioblastoma: Implications for Tumor Cell Resilience.Biochemical genetics · 2026Article
- Astrocyte-driven immunosuppression in the brain tumor microenvironment.Nature immunology · 2026Review
- Cancer Cell-Intrinsic Cholesterol Induces Lipid-Associated Macrophage Differentiation via SP1 Palmitoylation to Promote Prostate Cancer Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The Contribution of Cholesterol and Squalene Synthase in Cancer: Molecular Mechanisms, Lipid Rafts and Therapeutic Approaches.Medicinal research reviews · 2026Review
- Overcoming Chemoresistance in Glioblastoma: Mechanisms, Therapeutic Strategies, and Functional Precision Medicine.International journal of molecular sciences · 2026Review
- Targeting Metabolic Vulnerabilities in Glioblastoma: a Framework for Multi-node Combination Therapy.Current oncology reports · 2026Review
- Pan-cancer analysis of cholesterol metabolism reveals the uptake as a modulator of tumor immune features and of the KRAS pathway.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Adaptaquin is selectively toxic to glioma stem cells through disruption of iron and cholesterol metabolism.Molecular oncology · 2026Article
- Activated astrocytes drive the accumulation of apolipoprotein E at the brain tumor edge.Brain tumor pathology · 2026Article
- Metabolic remodeling and immune evasion in glioblastoma: a focus on serine and lipid networks.Frontiers in oncology · 2026Review
- Lipid metabolic plasticity in glioblastoma: mechanisms, tumor microenvironment remodeling, and therapeutic opportunities.Frontiers in oncology · 2026Review
154 more citing papers are in PubMed but not listed here.
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Authors and funding
27 authors at 7 institutions in 2 countries.
Genaro R VillaDepartment of Molecular and Medical Pharmacology, David Geffen UCLA School of Medicine, Los Angeles, CA 90095, USA; Medical Scientist Training Program, David Geffen UCLA School of Medicine, Los Angeles, CA 90095, USA; Ludwig Institute for Cancer Research, University of California San Diego, La Jolla, CA 92093, USA.
Jonathan J HulceDepartment of Chemical Physiology, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Ciro ZancaLudwig Institute for Cancer Research, University of California San Diego, La Jolla, CA 92093, USA.
Junfeng BiLudwig Institute for Cancer Research, University of California San Diego, La Jolla, CA 92093, USA.
Shiro IkegamiLudwig Institute for Cancer Research, University of California San Diego, La Jolla, CA 92093, USA.
Gabrielle L CahillLudwig Institute for Cancer Research, University of California San Diego, La Jolla, CA 92093, USA.
Yuchao GuDepartment of Molecular and Medical Pharmacology, David Geffen UCLA School of Medicine, Los Angeles, CA 90095, USA; Ludwig Institute for Cancer Research, University of California San Diego, La Jolla, CA 92093, USA.
Kenneth M LumDepartment of Chemical Physiology, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Kenta MasuiDepartment of Pathology, Tokyo Women's Medical University, Tokyo 162-8666, Japan.
Huijun YangLudwig Institute for Cancer Research, University of California San Diego, La Jolla, CA 92093, USA.
Xin RongDepartment of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Cynthia HongDepartment of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Kristen M TurnerLudwig Institute for Cancer Research, University of California San Diego, La Jolla, CA 92093, USA.
Feng LiuLudwig Institute for Cancer Research, University of California San Diego, La Jolla, CA 92093, USA.
Gary C HonLudwig Institute for Cancer Research, University of California San Diego, La Jolla, CA 92093, USA.
David JenkinsSmall Molecule Discovery Program, Ludwig Institute for Cancer Research, University of California San Diego, La Jolla, CA 92093, USA.
Michael MartiniDepartment of Chemical Physiology, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Aaron M ArmandoDepartment of Pharmacology, UCSD School of Medicine, La Jolla, CA 92093, USA.
Oswald QuehenbergerDepartment of Pharmacology, UCSD School of Medicine, La Jolla, CA 92093, USA; Department of Medicine, UCSD School of Medicine, La Jolla, CA 92093, USA.
Timothy F CloughesyDepartment of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Frank B FurnariLudwig Institute for Cancer Research, University of California San Diego, La Jolla, CA 92093, USA; Department of Pathology, UCSD School of Medicine, La Jolla, CA 92093, USA; Moores Cancer Center, UCSD School of Medicine, La Jolla, CA 92093, USA.
Webster K CaveneeLudwig Institute for Cancer Research, University of California San Diego, La Jolla, CA 92093, USA; Department of Medicine, UCSD School of Medicine, La Jolla, CA 92093, USA; Moores Cancer Center, UCSD School of Medicine, La Jolla, CA 92093, USA.
Peter TontonozDepartment of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Howard Hughes Medical Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Timothy C GahmanSmall Molecule Discovery Program, Ludwig Institute for Cancer Research, University of California San Diego, La Jolla, CA 92093, USA.
Andrew K ShiauSmall Molecule Discovery Program, Ludwig Institute for Cancer Research, University of California San Diego, La Jolla, CA 92093, USA.
Benjamin F CravattDepartment of Chemical Physiology, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. Electronic address: cravatt@scripps.edu.
Paul S MischelLudwig Institute for Cancer Research, University of California San Diego, La Jolla, CA 92093, USA; Department of Pathology, UCSD School of Medicine, La Jolla, CA 92093, USA; Moores Cancer Center, UCSD School of Medicine, La Jolla, CA 92093, USA. Electronic address: pmischel@ucsd.edu.
Ludwig Cancer Research · USUniversity of California, San Diego · USScripps Research Institute · USUniversity of California, Los Angeles · USMoores Cancer CenterHoward Hughes Medical Institute · USTokyo Women's Medical University · JP
Funding
Genotypic Interactions in Brain Cancer HeterogeneityR01NS080939 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FURNARI, FRANK · 2012 to 2022
$3.5MThe role of mTORC2 in reprogramming cancer cell metabolismR01NS073831 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MISCHEL, PAUL S · 2011 to 2020
$3.4MGenotypic Interactions in Brain Cancer HeterogeneityR56NS080939 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FURNARI, FRANK · 2023 to 2023
$537kA Novel Approach to Treating Glioblastoma through Activation of the Liver X RecepF31CA186668 · NCI · LUDWIG INSTITUTE FOR CANCER RES LTD · PI VILLA, GENARO R. · 2014 to 2016
$104kNCI NIH HHS F31 CA186668NINDS NIH HHS R01 NS073831NINDS NIH HHS R01 NS080939NINDS NIH HHS R56 NS080939
Abstract
Small-molecule inhibitors targeting growth factor receptors have failed to show efficacy for brain cancers, potentially due to their inability to achieve sufficient drug levels in the CNS. Targeting non-oncogene tumor co-dependencies provides an alternative approach, particularly if drugs with high brain penetration can be identified. Here we demonstrate that the highly lethal brain cancer glioblastoma (GBM) is remarkably dependent on cholesterol for survival, rendering these tumors sensitive to Liver X receptor (LXR) agonist-dependent cell death. We show that LXR-623, a clinically viable, highly brain-penetrant LXRα-partial/LXRβ-full agonist selectively kills GBM cells in an LXRβ- and cholesterol-dependent fashion, causing tumor regression and prolonged survival in mouse models. Thus, a metabolic co-dependency provides a pharmacological means to kill growth factor-activated cancers in the CNS.
Indexed as
AnimalsBrain NeoplasmsCell Line, TumorCell ProliferationCell SurvivalCholesterolFemaleGlioblastomaHumansIndazolesLiver X ReceptorsMiceTreatment Outcome2-(2-chloro-4-fluorobenzyl)-3-(4-fluorophenyl)-7-(trifluoromethyl)-2H-indazoleCholesterolIndazolesLiver X Receptorsbrain cancercholesterolglioblastomaliver X receptormetabolismoxysterols
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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.