ArticleCell death & disease2022
Pharmacological inhibition of Ref-1 enhances the therapeutic sensitivity of papillary thyroid carcinoma to vemurafenib.
Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 24 citations in OpenAlex.
- DNA Damage and Repair in Thyroid Physiology and Disease.Endocrine reviews · 2026Review
- Autophagy in thyroid cancer: stage-dependent switch, mutation-specific regulation, and therapeutic targeting.Oncology reviews · 2026Review
- Mechanisms and pathways of ROS and autophagy in thyroid cancer.Future science OA · 2025Review
- Progress in Drug-targeted Therapy for Papillary Thyroid Carcinoma.Current oncology reports · 2025Review
- Cellular senescence in cancer: from mechanism paradoxes to precision therapeutics.Molecular cancer · 2025Review
- Enhancer hijacking drives FAM20C expression to promote papillary thyroid cancer progression.Cancer gene therapy · 2025Article
- Review
- Article
- L-741626 inhibits hepatocellular carcinoma progression by targeting Ref-1 to suppress MAPK/ERK signalling pathway activity.Biology direct · 2025Article
- Personalized prediction of anticancer potential of non-oncology drugs through learning from genome derived molecular pathways.NPJ precision oncology · 2025Article
- Fucoidan Oligosaccharide Supplementation Relieved Kidney Injury and Modulated Intestinal Homeostasis in D-Galactose-Exposed Rats.Nutrients · 2025Article
- Papillary thyroid cancer and cutaneous melanoma: An often underrecognized pair.JAAD case reports · 2024Article
- Advances in the molecular mechanism and targeted therapy of radioactive-iodine refractory differentiated thyroid cancer.Medical oncology (Northwood, London, England) · 2023Review
- The new insights into autophagy in thyroid cancer progression.Journal of translational medicine · 2023Review
- Targeting Aurora-A inhibits tumor progression and sensitizes thyroid carcinoma to Sorafenib by decreasing PFKFB3-mediated glycolysis.Cell death & disease · 2023Article
- Article
- Disulfiram/Cu Kills and SensitizesInternational journal of molecular sciences · 2023Article
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 3 institutions in 1 country.
Funding
Abstract
The use of the BRAF inhibitor vemurafenib exhibits drug resistance in the treatment of thyroid cancer (TC), and finding more effective multitarget combination therapies may be an important solution. In the present study, we found strong correlations between Ref-1 high expression and BRAF mutation, lymph node metastasis, and TNM stage. The oxidative stress environment induced by structural activation of BRAF upregulates the expression of Ref-1, which caused intrinsic resistance of PTC to vemurafenib. Combination inhibition of the Ref-1 redox function and BRAF could enhance the antitumor effects of vemurafenib, which was achieved by blocking the action of Ref-1 on BRAF proteins. Furthermore, combination treatment could cause an overload of autophagic flux via excessive AMPK protein activation, causing cell senescence and cell death in vitro. And combined administration of Ref-1 and vemurafenib in vivo suppressed PTC cell growth and metastasis in a cell-based lung metastatic tumor model and xenogeneic subcutaneous tumor model. Collectively, our study provides evidence that Ref-1 upregulation via constitutive activation of BRAF in PTC contributes to intrinsic resistance to vemurafenib. Combined treatment with a Ref-1 redox inhibitor and a BRAF inhibitor could make PTC more sensitive to vemurafenib and enhance the antitumor effects of vemurafenib by further inhibiting the MAPK pathway and activating the excessive autophagy and related senescence process.
Indexed as
Identifiers
What OpenQuestion holds
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.