ArticleMolecular cancer2009
Sorafenib blocks tumour growth, angiogenesis and metastatic potential in preclinical models of osteosarcoma through a mechanism potentially involving the inhibition of ERK1/2, MCL-1 and ezrin pathways.
Article in Molecular cancer, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers, 2 of them syntheses that pooled it.
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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
92 citing papers in PubMed, 2 syntheses or guidelines pooled it, 176 citations in OpenAlex.
- Correlations of ezrin expression with pathological characteristics and prognosis of osteosarcoma: a meta-analysis.TheScientificWorldJournal · 2014Pooled it
- The prognostic value of elevated vascular endothelial growth factor in patients with osteosarcoma: a meta-analysis and systemic review.Journal of cancer research and clinical oncology · 2012Pooled it
- Trial
- Integrative single-cell analysis reveals immunogenic cell death-associated heterogeneity and identifies a robust prognostic signature in osteosarcoma with experimental validation.Frontiers in pharmacology · 2026Article
- Matrix type influences embedded patient-derived osteosarcoma organoid invasion and response to treatment.Frontiers in pharmacology · 2026Article
- Advancements in Osteosarcoma Therapy: Overcoming Chemotherapy Resistance and Exploring Novel Pharmacological Strategies.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Targeting the EphA2 pathway: could it be the way for bone sarcomas?Cell communication and signaling : CCS · 2024Review
- Ezrin's role in gastric cancer progression: Implications for immune microenvironment modulation and therapeutic potential.Heliyon · 2024Article
- Host-derived growth factors drive ERK phosphorylation and MCL1 expression to promote osteosarcoma cell survival during metastatic lung colonization.Cellular oncology (Dordrecht, Netherlands) · 2024Article
- Targeted anti-angiogenesis therapy for advanced osteosarcoma.Frontiers in oncology · 2024Review
- Improving Osteosarcoma Treatment: Comparative Oncology in Action.Life (Basel, Switzerland) · 2022Article
- Discovery of synthetic lethal interactions from large-scale pan-cancer perturbation screens.Nature communications · 2022Article
- Multi-omics analysis based on 3D-bioprinted models innovates therapeutic target discovery of osteosarcoma.Bioactive materials · 2022Article
- Receptor Tyrosine Kinase Inhibitors for the Treatment of Recurrent and Unresectable Bone Sarcomas.International journal of molecular sciences · 2022Review
- Cytoskeletal and Cytoskeleton-Associated Proteins: Key Regulators of Cancer Stem Cell Properties.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Chemoresistance-Related Stem Cell Signaling in Osteosarcoma and Its Plausible Contribution to Poor Therapeutic Response: A Discussion That Still Matters.International journal of molecular sciences · 2022Review
- Mass Spectrometric-Based Proteomics for Biomarker Discovery in Osteosarcoma: Current Status and Future Direction.International journal of molecular sciences · 2022Review
- Sorafenib and Doxorubicin Show Synergistic Effects in Human and Canine Osteosarcoma Cell Lines.International journal of molecular sciences · 2022Article
- Origin and Therapies of Osteosarcoma.Cancers · 2022Review
- Chidamide augment sorafenib-derived anti-tumor activities in human osteosarcoma cells lines and xenograft mouse model.Medical oncology (Northwood, London, England) · 2022Article
32 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundOsteosarcoma (OS) is the most common primary bone tumour in children and young adults. Despite improved prognosis, metastatic or relapsed OS remains largely incurable and no significant improvement has been observed in the last 20 years. Therefore, the search for alternative agents in OS is mandatory.
resultsWe investigated phospho-ERK 1/2, MCL-1, and phospho-Ezrin/Radixin/Moesin (P-ERM) as potential therapeutic targets in OS. Activation of these pathways was shown by immunohistochemistry in about 70% of cases and in all OS cell lines analyzed. Mutational analysis revealed no activating mutations in KRAS whereas BRAF gene was found to be mutated in 4/30 OS samples from patients. Based on these results we tested the multi-kinase inhibitor sorafenib (BAY 43-9006) in preclinical models of OS. Sorafenib inhibited OS cell line proliferation, induced apoptosis and downregulated P-ERK1/2, MCL-1, and P-ERM in a dose-dependent manner. The dephosphorylation of ERM was not due to ERK inhibition. The downregulation of MCL-1 led to an increase in apoptosis in OS cell lines. In chick embryo chorioallantoic membranes, OS supernatants induced angiogenesis, which was blocked by sorafenib and it was also shown that sorafenib reduced VEGF and MMP2 production. In addition, sorafenib treatment dramatically reduced tumour volume of OS xenografts and lung metastasis in SCID mice.
conclusionIn conclusion, ERK1/2, MCL-1 and ERM pathways are shown to be active in OS. Sorafenib is able to inhibit their signal transduction, both in vitro and in vivo, displaying anti-tumoural activity, anti-angiogenic effects, and reducing metastatic colony formation in lungs. These data support the testing of sorafenib as a potential therapeutic option in metastatic or relapsed OS patients unresponsive to standard treatments.
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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.