ArticleNature communications2023
Regorafenib inhibits EphA2 phosphorylation and leads to liver damage via the ERK/MDM2/p53 axis.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- A Systematic Review and Meta-Analysis of the Efficacy and Safety of Regorafenib in the Treatment of Metastatic Colorectal Cancer.Journal of gastrointestinal cancer · 2024Pooled it
- CD22Science China. Life sciences · 2026Article
- Pseudorabies virus pUL40 drives inflammatory signaling through competitive hijacking of EphA2 from the Akt-EphA2 interaction.Veterinary research · 2026Article
- Article
- Paeoniflorin Alleviates Coronary Artery Lesions in Kawasaki Disease by Activating NRF2 Pathway and Inhibiting CYP2E1 Expression.Cardiovascular drugs and therapy · 2026Article
- Hyaluronic acid capped cubosomes co-loaded with antitumor agents towards the treatment of colorectal cancer.Scientific reports · 2025Article
- Wuweizisu B for cancer treatment from multitarget mechanisms to precision delivery strategies (Review).International journal of molecular medicine · 2025Review
- The PLEKHA1-TACC2 fusion gene drives tumorigenesis via vascular mimicry formation in esophageal squamous-cell carcinoma.Cell death and differentiation · 2025Article
- Uncovering the anti-cervical cancer mechanism of Ziyuglycoside I via integrated network pharmacology molecular docking and experimental validation.Scientific reports · 2025Article
- Development and challenges in the treatment of advanced gallbladder cancer (Review).Oncology letters · 2025Review
- Genome-wide enhancer-gene regulatory maps of liver reveal novel regulatory mechanisms underlying NAFLD pathogenesis.BMC genomics · 2025Article
- Disturbing Cholesterol/Sphingolipid Metabolism by Squalene Epoxidase Arises Crizotinib Hepatotoxicity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Quercetin reverses βFrontiers in nutrition · 2025Article
- 5-O-Methylvisammioside inhibits HMGB1-induced Angiogenesis of hepatocellular carcinoma through RAGE/MEK/ERK signaling pathway.PloS one · 2025Article
- Eph receptor signaling complexes in the plasma membrane.Trends in biochemical sciences · 2024Review
- Eph receptors and ephrins in cancer progression.Nature reviews. Cancer · 2024Review
- Gut microbiota depletion and FXR inhibition exacerbates zonal hepatotoxicity of sunitinib.Theranostics · 2024Article
- Metformin Suppresses Stemness of Non-Small-Cell Lung Cancer Induced by Paclitaxel through FOXO3a.International journal of molecular sciences · 2023Article
- [Strategies for liver injury caused by hepatocellular carcinoma targeted therapy].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2023Article
- Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The hepatotoxicity of regorafenib is one of the most noteworthy concerns for patients, however the mechanism is poorly understood. Hence, there is a lack of effective intervention strategies. Here, by comparing the target with sorafenib, we show that regorafenib-induced liver injury is mainly due to its nontherapeutic target Eph receptor A2 (EphA2). EphA2 deficiency attenuated liver damage and cell apoptosis under regorafenib treatment in male mice. Mechanistically, regorafenib inhibits EphA2 Ser897 phosphorylation and reduces ubiquitination of p53 by altering the intracellular localization of mouse double minute 2 (MDM2) by affecting the extracellular signal-regulated kinase (ERK)/MDM2 axis. Meanwhile, we found that schisandrin C, which can upregulate the phosphorylation of EphA2 at Ser897 also has protective effect against the toxicity in vivo. Collectively, our findings identify the inhibition of EphA2 Ser897 phosphorylation as a key cause of regorafenib-induced hepatotoxicity, and chemical activation of EphA2 Ser897 represents a potential therapeutic strategy to prevent regorafenib-induced hepatotoxicity.
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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.