ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2023
Donafenib and GSK-J4 Synergistically Induce Ferroptosis in Liver Cancer by Upregulating HMOX1 Expression.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 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.
The trial behind it
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Who cites it
86 citing papers in PubMed, 118 citations in OpenAlex.
- Single-cell transcriptomics identifies PRDX1 and GPX4 as potential ferroptosis regulators and tumor microenvironment--related molecules in hepatocellular carcinoma.Oncology letters · 2026Article
- YTHDF2 drives malignant progression in cutaneous melanoma through m⁶A-dependent HMOX1-mediated ferroptosis.Medical oncology (Northwood, London, England) · 2026Article
- Ferroptosis in cancer: molecular mechanisms, biological roles, and therapeutic significance.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- scRNA-seq and bulk RNA-seq reveal the characteristics of macrophage copper metabolism and establish a risk signature in hepatocellular carcinoma.Translational cancer research · 2026Article
- HMOX1 controls a heme-ferritin switch that protects cells from ferroptosis.Science advances · 2026Article
- Blood-brain barrier-penetrant nanotherapy inhibits haem oxygenase-1-mediated ferroptosis for post-resuscitation neuroprotection.Nature communications · 2026Article
- Evolving Landscape of Systemic Therapy for Hepatocellular Carcinoma: From Targeted Therapy and Combination Strategies to Emerging Therapies.Biomedicines · 2026Review
- Covalent Inhibition of SHMT2 by Gambogic Acid Induces Ferroptosis Through Mitochondrial Collapse in Triple-Negative Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Metabolic Mechanisms of Hexavalent Chromium-Induced Splenic Immune Injury via Oxidative Stress and Ferroptosis Pathways in New Zealand Rabbits.Metabolites · 2026Article
- Tipping the balance: NRF2's dual role in ferroptotic fate.Oncogenesis · 2026Review
- GSK-J4 Suppresses Tumorigenesis by Targeting the PERK-c-Myc Pathway Through Endoplasmic Reticulum Stress Activation in Tuberous Sclerosis Complex.International journal of molecular sciences · 2026Article
- IRX4204 sensitizes multiple myeloma to ferroptosis and improves lenalidomide efficacy through the HMOX1-GPX4 axis.Scientific reports · 2026Article
- TROP2 confers resistance to oxidative stress-induced cancer cell death through YAP/HMOX1 signaling.Journal of translational medicine · 2026Article
- From mechanism to clinic: a panoramic perspective on targeting HMOX1 to overcome drug resistance.Journal of cancer research and clinical oncology · 2026Review
- ERM Inhibition Confers Ferroptosis Resistance through ROS-Induced NRF2 Signaling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Combinatorial treatment with donafenib and quercetin suppresses lipid metabolism in HepG2 cells by targeting the CREB1/DRP1/SREBP1 axis.Translational cancer research · 2026Article
- KLF1 Exerts Pro-Tumour Role in Liver Cancer via Inhibiting ACSL4/LPCAT3-Regulated Ferroptosis.Journal of cellular and molecular medicine · 2026Article
- Integrating machine learning and multi-omics analysis to explore Treg-associated programmed cell death features in clear cell renal cell carcinoma.Cancer cell international · 2026Article
- Post-translational modifications in retinoblastoma: mechanisms, immune regulation, and therapeutic opportunities.Frontiers in immunology · 2026Review
- Protective effect of a novel hydrogel loaded with CM-UCMSCs on vitrified-thawed ovaries during in vitro culture.Frontiers in bioengineering and biotechnology · 2026Article
26 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide. Donafenib is a multi-receptor tyrosine kinase inhibitor approved for the treatment of patients with advanced HCC, but its clinical effect is very limited. Here, through integrated screening of a small-molecule inhibitor library and a druggable CRISPR library, that GSK-J4 is synthetically lethal with donafenib in liver cancer is shown. This synergistic lethality is validated in multiple HCC models, including xenograft, orthotopically induced HCC, patient-derived xenograft, and organoid models. Furthermore, co-treatment with donafenib and GSK-J4 resulted in cell death mainly via ferroptosis. Mechanistically, through integrated RNA sequencing (RNA-seq) and assay for transposase-accessible chromatin with high throughput sequencing (ATAC-seq) analyses, that donafenib and GSK-J4 synergistically promoted the expression of HMOX1 and increased the intracellular Fe2+ level is found, eventually leading to ferroptosis. Additionally, through cleavage under targets & tagmentation followed by sequencing (CUT&Tag-seq), it is found that the enhancer regions upstream of HMOX1 promoter significantly increased under donafenib and GSK-J4 co-treatment. A chromosome conformation capture assay confirmed that the increased expression of HMOX1 is caused by the significantly enhanced interaction between the promoter and upstream enhancer under dual-drug combination. Taken together, this study elucidates a new synergistic lethal interaction in liver cancer.
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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.