ArticleJournal of cellular and molecular medicine2015
Synergistic antitumour activity of RAF265 and ZSTK474 on human TT medullary thyroid cancer cells.
Article in Journal of cellular and molecular medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 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.
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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.
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Who cites it
13 citing papers in PubMed, 21 citations in OpenAlex.
- Imidazole-Functionalized Thieno[3,2-c]Quinoline Hybrids in Aggressive Medullary Thyroid Cancer Cell Models: Biological Evaluation and in Silico Insights.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Identification and validation of mitochondrial and programmed cell death-related prognostic markers in pediatric acute myeloid leukemia.Frontiers in immunology · 2025Article
- Review
- Review
- Review
- Review
- Update on Targeted Therapy in Medullary Thyroid Cancer.Frontiers in endocrinology · 2021Review
- Combinatorial Therapies in Thyroid Cancer: An Overview of Preclinical and Clinical Progresses.Cells · 2020Review
- The combination of Biochanin A and SB590885 potentiates the inhibition of tumour progression in hepatocellular carcinoma.Cancer cell international · 2020Article
- Anticancer Effects of Wild MountainFrontiers in pharmacology · 2019Article
- Synergistic activity of magnolin combined with B-RAF inhibitor SB590885 in hepatocellular carcinoma cells via targeting PI3K-AKT/mTOR and ERK MAPK pathway.American journal of translational research · 2019Article
- The aurora kinase inhibitor VX-680 shows anti-cancer effects in primary metastatic cells and the SW13 cell line.Investigational new drugs · 2016Article
- PI3K/AKT Pathway and Its Mediators in Thyroid Carcinomas.Molecular diagnosis & therapy · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Medullary thyroid cancer (MTC) is an aggressive malignancy responsible for up to 14% of all thyroid cancer-related deaths. It is characterized by point mutations in the rearranged during transfection (RET) proto-oncogene. The activated RET kinase is known to signal via extracellular signal regulated kinase (ERK) and phosphoinositide 3-kinase (PI3K), leading to enhanced proliferation and resistance to apoptosis. In the present work, we have investigated the effect of two serine/threonine-protein kinase B-Raf (BRAF) inhibitors (RAF265 and SB590885), and a PI3K inhibitor (ZSTK474), on RET-mediated signalling and proliferation in a MTC cell line (TT cells) harbouring the RETC634W activating mutation. The effects of the inhibitors on VEGFR2, PI3K/Akt and mitogen-activated protein kinases signalling pathways, cell cycle, apoptosis and calcitonin production were also investigated. Only the RAF265+ ZSTK474 combination synergistically reduced the viability of treated cells. We observed a strong decrease in phosphorylated VEGFR2 for RAF265+ ZSTK474 and a signal reduction in activated Akt for ZSTK474. The activated ERK signal also decreased after RAF265 and RAF265+ ZSTK474 treatments. Alone and in combination with ZSTK474, RAF265 induced a sustained increase in necrosis. Only RAF265, alone and combined with ZSTK474, prompted a significant drop in calcitonin production. Combination therapy using RAF265 and ZSTK47 proved effective in MTC, demonstrating a cytotoxic effect. As the two inhibitors have been successfully tested individually in clinical trials on other human cancers, our preclinical data support the feasibility of their combined use in aggressive MTC.
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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.