ArticleCancer discovery2021
Cholesterol Auxotrophy as a Targetable Vulnerability in Clear Cell Renal Cell Carcinoma.
Article in Cancer discovery, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers, 2 of them syntheses that pooled it.
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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.
The trial behind it
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
80 citing papers in PubMed, 2 syntheses or guidelines pooled it, 115 citations in OpenAlex.
- Genetic landscape and functional exploration of kidney cancer predisposition in cross-ancestral populations.Nature communications · 2026Pooled it
- Multi-ancestry genome-wide association study of kidney cancer identifies 63 susceptibility regions.Nature genetics · 2024Pooled it
- PDE5A Inhibition Restricts Cancer Metastasis by Disrupting NPC1-Mediated Cholesterol Trafficking through a Noncanonical cGMP-Dependent Pathway.Cancer research · 2026Article
- Metabolic reprogramming-mediated therapeutic resistance in renal cell carcinoma: Mechanisms and targeted intervention strategies.iScience · 2026Review
- Soulangianolide A targets FAM120A to disrupt SREBP1-driven lipid metabolic reprogramming and suppress clear cell renal cell carcinoma.Journal of experimental & clinical cancer research : CR · 2026Article
- CT-Based Radiomics for Prediction of Molecular Markers in Clear Cell Renal Cell Carcinoma: A Comprehensive Review.Medicina (Kaunas, Lithuania) · 2026Review
- Lactate-mediated cholesterol uptake promotes liver cancer progression via the SCARB1-autophagy axis.EMBO reports · 2026Article
- A network medicine framework for multi-modal data integration in therapeutic target discovery.Communications chemistry · 2026Article
- Review
- LDHA-driven ACAA2 lactylation at K270 reprograms fatty acid metabolism to promote clear cell renal cell carcinoma progression.Scientific reports · 2026Article
- PDZK1-ULK1 Axis Triggers Lipophagy to Inhibit Tumor Progression and Sunitinib Resistance in Clear Cell Renal Cell Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Phosphatidylserine transporters ORP5 and ORP8 control cholesterol trafficking from the plasma membrane to the endoplasmic reticulum.Journal of lipid research · 2026Article
- Generation of a comprehensive epigenomic atlas in clear cell renal cell carcinoma informs kidney cancer progression and heritability.Cell reports · 2026Article
- 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
- Systematic assessment of obesity-related risk factors in renal cancer etiology: A longitudinal risk and Mendelian randomization analysis.PLoS medicine · 2026Article
- Obesity-driven metabolic reprogramming and immune dysfunction in renal cancer.Frontiers in immunology · 2026Review
- Lipid metabolic reprogramming in clear cell renal cell carcinoma: focus on high-density lipoprotein-related pathways.Oncology reviews · 2026Review
- The GPR183-oxysterol axis in cancer: immune trafficking, spatial organization, and therapeutic potential.Frontiers in immunology · 2026Review
- Comprehensive analysis of fatty acid desaturase 3 in clear cell renal cell carcinoma: insights into tumor progression, immune microenvironment, and clinical outcomes.Frontiers in immunology · 2026Article
- Cholesterol metabolism and cancer: Molecular mechanisms, immune regulation and an epidemiological perspective (Review).International journal of molecular medicine · 2025Review
20 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
19 authors at 6 institutions in 3 countries.
Funding
Abstract
Clear cell renal cell carcinoma (ccRCC) is characterized by large intracellular lipid droplets containing free and esterified cholesterol; however, the functional significance of cholesterol accumulation in ccRCC cells is unknown. We demonstrate that, surprisingly, genes encoding cholesterol biosynthetic enzymes are repressed in ccRCC, suggesting a dependency on exogenous cholesterol. Mendelian randomization analyses based on 31,000 individuals indicate a causal link between elevated circulating high-density lipoprotein (HDL) cholesterol and ccRCC risk. Depriving ccRCC cells of either cholesterol or HDL compromises proliferation and survival in vitro and tumor growth in vivo; in contrast, elevated dietary cholesterol promotes tumor growth. Scavenger Receptor B1 (SCARB1) is uniquely required for cholesterol import, and inhibiting SCARB1 is sufficient to cause ccRCC cell-cycle arrest, apoptosis, elevated intracellular reactive oxygen species levels, and decreased PI3K/AKT signaling. Collectively, we reveal a cholesterol dependency in ccRCC and implicate SCARB1 as a novel therapeutic target for treating kidney cancer. SIGNIFICANCE: We demonstrate that ccRCC cells are auxotrophic for exogenous cholesterol to maintain PI3K/AKT signaling pathway and ROS homeostasis. Blocking cholesterol import through the HDL transporter SCARB1 compromises ccRCC cell survival and tumor growth, suggesting a novel pharmacologic target for this disease. This article is highlighted in the In This Issue feature, p. 2945.
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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.