ArticleCell death & disease2017
Increasing AR by HIF-2α inhibitor (PT-2385) overcomes the side-effects of sorafenib by suppressing hepatocellular carcinoma invasion via alteration of pSTAT3, pAKT and pERK signals.
Article in Cell death & disease, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 72 citations in OpenAlex.
- Chronic cerebral hypoperfusion induces venous dysfunction via EPAS1 regulation in mice.Nature communications · 2025Article
- Bridging Immune Evasion and Vascular Dynamics for Novel Therapeutic Frontiers in Hepatocellular Carcinoma.Cancers · 2025Review
- Cancer stem cells in hepatocellular carcinoma: therapy resistance and emerging treatments.Frontiers in immunology · 2025Review
- Review
- Hypoxia as a Target for Combination with Transarterial Chemoembolization in Hepatocellular Carcinoma.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Testosterone Exacerbates the Formation of Liver Cancer Induced by Environmental N-Nitrosamines Exposure: Potential Mechanisms and Implications for Human Health.OncoTargets and therapy · 2024Article
- Novel cancer treatment paradigm targeting hypoxia-induced factor in conjunction with current therapies to overcome resistance.Journal of experimental & clinical cancer research : CR · 2023Review
- Spontaneous spheroids from alveolar bone-derived mesenchymal stromal cells maintain pluripotency of stem cells by regulating hypoxia-inducible factors.Biological research · 2023Article
- The Roles of Epigenetic Regulation and the Tumor Microenvironment in the Mechanism of Resistance to Systemic Therapy in Hepatocellular Carcinoma.International journal of molecular sciences · 2023Review
- The current status of tumor microenvironment and cancer stem cells in sorafenib resistance of hepatocellular carcinoma.Frontiers in oncology · 2023Review
- Androgen Receptor Expression in the Various Regions of Resected Glioblastoma Multiforme Tumors and in an In Vitro Model.International journal of molecular sciences · 2022Article
- The hypoxia-driven crosstalk between tumor and tumor-associated macrophages: mechanisms and clinical treatment strategies.Molecular cancer · 2022Review
- Novel insights into roles of N6-methyladenosine reader YTHDF2 in cancer progression.Journal of cancer research and clinical oncology · 2022Review
- Prognostic comparative genes predict targets for sorafenib combination therapies in hepatocellular carcinoma.Computational and structural biotechnology journal · 2022Article
- Co-delivery of sorafenib and metformin from amphiphilic polypeptide-based micelles for colon cancer treatment.Frontiers in medicine · 2022Article
- Article
- Review
- UBQLN1 mediates sorafenib resistance through regulating mitochondrial biogenesis and ROS homeostasis by targeting PGC1β in hepatocellular carcinoma.Signal transduction and targeted therapy · 2021Article
- Critical signaling pathways governing hepatocellular carcinoma behavior; small molecule-based approaches.Cancer cell international · 2021Review
- Development of an Aerobic Glycolysis Index for Predicting the Sorafenib Sensitivity and Prognosis of Hepatocellular Carcinoma.Frontiers in oncology · 2021Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although sorafenib is currently used as a standard treatment for advanced hepatocellular carcinoma, low response rate, transient and limited efficacy, primary and acquired resistance and negative side-effects gain increasing attentions, suggesting the need for better efficacious combination therapy. Here, we demonstrated that the sorafenib-induced or hypoxia-induced hypoxia inducible factor (HIF)-2α could bind to an hypoxia responsive element within 500 bp region of androgen receptor (AR) promoter and thus transcriptionally suppress AR. Importantly, In vitro and In vivo studies suggested a specific and potent HIF-2α inhibitor, PT-2385, could significantly enhance sorafenib efficacy by suppressing HIF-2α, increasing AR and suppressing downstream pSTAT3/pAKT/pERK pathways. Clinical samples further confirmed the role of HIF-2α and AR. It is promising that PT-2385 could alleviate the undesirable side-effects of sorafenib treatment by sorafenib-PT-2385 combination therapy, which may shed light for late-stage HCC patients.
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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.