ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2024
Nanoparticle Targeting in Chemo-Resistant Ovarian Cancer Reveals Dual Axis of Therapeutic Vulnerability Involving Cholesterol Uptake and Cell Redox Balance.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 24 citations in OpenAlex.
- Nanotherapeutics for enhanced treatments for ovarian cancer: a comprehensive minireview.Drug delivery · 2026Review
- Regulation of lipid oxidation and ferroptosis by a tunable axis of vitamin E, high-density lipoprotein, and scavenger receptor class B type 1.The Journal of biological chemistry · 2026Article
- GPX4 in the Tumor Microenvironment: Not Just Inhibiting Ferroptosis, but Immuno-Metabolic Regulation.Biomolecules · 2026Review
- Acetylation in ovarian cancer: mechanistic insights into drug resistance and emerging therapeutic opportunities.Journal of ovarian research · 2026Review
- Cholesterol-driven mitochondrial rejuvenation by quercetin nanotherapeutics restores implant osseointegration in diabetes.Bioactive materials · 2026Article
- Oleic acid fuels cisplatin-resistant ovarian cancer through FABP4-driven lipid uptake.Molecular metabolism · 2026Article
- Spatial habitats radiomics from multiparametric magnetic resonance imaging predict platinum resistance in epithelial ovarian cancer.Journal of ovarian research · 2026Article
- Platinum-resistant ovarian cancer: From mechanisms to treatment strategies.Genes & diseases · 2026Review
- Epitranscriptomic Regulation of Platinum Resistance via the METTL3-ADAM23 Axis in Ovarian Cancer.Cells · 2026Article
- Metabolic Dependency on De Novo Pyrimidine Synthesis Is a Targetable Vulnerability in Platinum-Resistant Ovarian Cancer.Cancer research · 2026Article
- Post-translational modifications in ferroptosis: mechanisms and therapeutic potential.International journal of biological sciences · 2026Review
- OMNIS: a spatially informed multi-omics deep-learning framework for tumor recurrence prediction and primary-metastatic tumor differentiation title page.Frontiers in artificial intelligence · 2026Article
- Advances in ferroptosis research in ovarian cancer: molecular mechanisms and therapeutic perspectives.American journal of cancer research · 2026Review
- Role of the tumor microenvironment in chemotherapy resistance in ovarian cancer and targeted therapy.Journal of ovarian research · 2025Review
- Advanced multifunctional nano-delivery platform focusing on treating diseases related to lipid metabolism via targeted intervention in various lipid metabolic processes.Military Medical Research · 2025Review
- Cholesterol metabolism and cancer: Molecular mechanisms, immune regulation and an epidemiological perspective (Review).International journal of molecular medicine · 2025Review
- Exploring the Impact of Nanotherapeutics on Histone H3 and H4 Acetylation Enrichment in Cancer Epigenome: A Systematic Scoping Synthesis.Epigenomes · 2025Review
- Targeting scavenger receptor class B type 1 with a bioinspired ligand induces apoptosis or ferroptosis in AML.Blood neoplasia · 2025Article
- Clinical insight-driven micron-sized cholesterol oxidation platform for membrane lipid therapy of advanced ovarian cancer.Journal of nanobiotechnology · 2025Article
- Dual-ferroptosis induction-based microneedle patches for enhanced chemodynamic/photothermal combination therapy against triple-negative breast cancer.Acta pharmaceutica Sinica. B · 2025Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Platinum (Pt)-based chemotherapy is the main treatment for ovarian cancer (OC); however, most patients develop Pt resistance (Pt-R). This work shows that Pt-R OC cells increase intracellular cholesterol through uptake via the HDL receptor, scavenger receptor type B-1 (SR-B1). SR-B1 blockade using synthetic cholesterol-poor HDL-like nanoparticles (HDL NPs) diminished cholesterol uptake leading to cell death and inhibition of tumor growth. Reduced cholesterol accumulation in cancer cells induces lipid oxidative stress through the reduction of glutathione peroxidase 4 (GPx4) leading to ferroptosis. In turn, GPx4 depletion induces decreased cholesterol uptake through SR-B1 and re-sensitizes OC cells to Pt. Mechanistically, GPx4 knockdown causes lower expression of the histone acetyltransferase EP300, leading to reduced deposition of histone H3 lysine 27 acetylation (H3K27Ac) on the sterol regulatory element binding transcription factor 2 (SREBF2) promoter and suppressing expression of this key transcription factor involved in the regulation of cholesterol metabolism. SREBF2 downregulation leads to decreased SR-B1 expression and diminished cholesterol uptake. Thus, chemoresistance and cancer cell survival under high ROS burden obligates high GPx4 and SR-B1 expression through SREBF2. Targeting SR-B1 to modulate cholesterol uptake inhibits this axis and causes ferroptosis in vitro and in vivo in Pt-R OC.
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