ArticleNeoplasia (New York, N.Y.)2014
SC-2001 overcomes STAT3-mediated sorafenib resistance through RFX-1/SHP-1 activation in hepatocellular carcinoma.
Article in Neoplasia (New York, N.Y.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 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
36 citing papers in PubMed, 45 citations in OpenAlex.
- Regulatory factor X1 promotes sorafenib-induced ferroptosis in hepatocellular carcinoma by transcriptional regulation of BECN1.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- RFX1 Regulates Immune Microenvironment and Predicts Immunotherapy Response in Colon Cancer: A Multi-Omics and Clinical Analysis.Oncology research · 2025Article
- Deciphering STAT3 signaling potential in hepatocellular carcinoma: tumorigenesis, treatment resistance, and pharmacological significance.Cellular & molecular biology letters · 2023Review
- Article
- Hypoxia-induced exosomes facilitate lung pre-metastatic niche formation in hepatocellular carcinoma through the miR-4508-RFX1-IL17A-p38 MAPK-NF-κB pathway.International journal of biological sciences · 2023Article
- Potential Treatment Strategies for Hepatocellular Carcinoma Cell Sensitization to Sorafenib.Journal of hepatocellular carcinoma · 2023Review
- HMGCS2 Mediation of Ketone Levels Affects Sorafenib Treatment Efficacy in Liver Cancer Cells.Molecules (Basel, Switzerland) · 2022Article
- Small Molecule Inhibitors for Hepatocellular Carcinoma: Advances and Challenges.Molecules (Basel, Switzerland) · 2022Review
- STAT3 pathway in cancers: Past, present, and future.MedComm · 2022Review
- Therapeutic effects of TM4SF5-targeting chimeric and humanized monoclonal antibodies in hepatocellular and colon cancer models.Molecular therapy oncolytics · 2022Article
- Article
- Article
- The phosphatase Shp1 interacts with and dephosphorylates cortactin to inhibit invadopodia function.Cell communication and signaling : CCS · 2021Article
- RFX1: a promising therapeutic arsenal against cancer.Cancer cell international · 2021Review
- Sorafenib and CuB exert synergistic antitumor effects against hepatocellular carcinoma cells via inhibition of STAT3 phosphorylation.FEBS open bio · 2021Article
- Long Noncoding RNA RMRP Suppresses the Tumorigenesis of Hepatocellular Carcinoma Through Targeting microRNA-766.OncoTargets and therapy · 2020Article
- Treatment with a new benzimidazole derivative bearing a pyrrolidine side chain overcomes sorafenib resistance in hepatocellular carcinoma.Scientific reports · 2019Article
- Regorafenib reverses HGF-induced sorafenib resistance by inhibiting epithelial-mesenchymal transition in hepatocellular carcinoma.FEBS open bio · 2019Article
- Antrodia cinnamomea boosts the anti-tumor activity of sorafenib in xenograft models of human hepatocellular carcinoma.Scientific reports · 2018Article
- 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
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatocellular carcinoma is the fifth most common solid cancer worldwide. Sorafenib, a small multikinase inhibitor, is the only approved therapy for advanced HCC. The clinical benefit of sorafenib is offset by the acquisition of sorafenib resistance. Understanding of the molecular mechanism of STAT3 overexpression in sorafenib resistance is critical if the clinical benefits of this drug are to be improved. In this study, we explored our hypothesis that loss of RFX-1/SHP-1 and further increase of p-STAT3 as a result of sorafenib treatment induces sorafenib resistance as a cytoprotective response effect, thereby, limiting sorafenib sensitivity and efficiency. We found that knockdown of RFX-1 protected HCC cells against sorafenib-induced cell apoptosis and SHP-1 activity was required for the process. SC-2001, a molecule with similar structure to obatoclax, synergistically suppressed tumor growth when used in combination with sorafenib in vitro and overcame sorafenib resistance through up-regulating RFX-1 and SHP-1 resulting in tumor suppression and mediation of dephosphorylation of STAT3. In addition, sustained sorafenib treatment in HCC led to increased p-STAT3 which was a key mediator of sorafenib sensitivity. The combination of SC-2001 and sorafenib strongly inhibited tumor growth in both wild-type and sorafenib-resistant HCC cell bearing xenograft models. These results demonstrate that inactivation of RFX/SHP-1 induced by sustained sorafenib treatment confers sorafenib resistance to HCC through p-STAT3 up-regulation. These effects can be overcome by SC-2001 through RFX-1/SHP-1 dependent p-STAT3 suppression. In conclusion, the use of SC-2001 in combination with sorafenib may constitute a new strategy for HCC therapy.
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.