ArticleRadiation oncology (London, England)2009
The c-Met receptor tyrosine kinase inhibitor MP470 radiosensitizes glioblastoma cells.
Article in Radiation oncology (London, England), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 114 citations in OpenAlex.
- Capmatinib is an effective treatment for MET-fusion driven pediatric high-grade glioma and synergizes with radiotherapy.Molecular cancer · 2024Article
- Immunological and tumor-intrinsic mechanisms mediate the synergistic growth suppression of experimental glioblastoma by radiotherapy and MET inhibition.Acta neuropathologica communications · 2023Article
- The benefit of co-targeting PARP-1 and c-Met on the efficacy of radiotherapy in wild type BRAF melanoma.Frontiers in medicine · 2023Article
- An oncogene addiction phosphorylation signature and its derived scores inform tumor responsiveness to targeted therapies.Cellular and molecular life sciences : CMLS · 2022Article
- The DNA Double-Strand Break Repair in Glioma: Molecular Players and Therapeutic Strategies.Molecular neurobiology · 2022Review
- Targeting RAD51-Mediated Homologous Recombination as a Treatment for Advanced Solid and Hematologic Malignancies: Opportunities and Challenges Ahead.OncoTargets and therapy · 2022Review
- Expression Levels of RAD51 Inversely Correlate with Survival of Glioblastoma Patients.Cancers · 2021Article
- Novel Receptor Tyrosine Kinase Pathway Inhibitors for Targeted Radionuclide Therapy of Glioblastoma.Pharmaceuticals (Basel, Switzerland) · 2021Review
- DNA Repair Mechanisms and Therapeutic Targets in Glioma.Current oncology reports · 2021Review
- Late p65 nuclear translocation in glioblastoma cells indicates non-canonical TLR4 signaling and activation of DNA repair genes.Scientific reports · 2021Article
- c-Met expression in renal cell carcinoma with bone metastases.Journal of bone oncology · 2020Review
- Deciphering MET-dependent modulation of global cellular responses to DNA damage by quantitative phosphoproteomics.Molecular oncology · 2020Article
- The Amuvatinib Derivative, N-(2H-1,3-Benzodioxol-5-yl)-4-{thieno[3,2-d]pyrimidin-4-yl}piperazine-1-carboxamide, Inhibits Mitochondria and Kills Tumor Cells under Glucose Starvation.International journal of molecular sciences · 2020Article
- AXL receptor tyrosine kinase as a promising anti-cancer approach: functions, molecular mechanisms and clinical applications.Molecular cancer · 2019Review
- Article
- Glioblastoma Multiforme: An Overview of Emerging Therapeutic Targets.Frontiers in oncology · 2019Review
- Negative control of the HGF/c-MET pathway by TGF-β: a new look at the regulation of stemness in glioblastoma.Cell death & disease · 2017Article
- Article
- Review
- Foretinib Enhances the Radiosensitivity in Esophageal Squamous Cell Carcinoma by Inhibiting Phosphorylation of c-Met.Journal of Cancer · 2017Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeGlioblastoma multiforme (GBM) is resistant to current cytotoxic therapies, in part because of enhanced DNA repair. Activation of the receptor tyrosine kinase c-Met has been shown to protect cancer cells from DNA damage. We hypothesized that inhibiting c-Met would decrease this protection and thus sensitize resistant tumor cells to the effects of radiation therapy. MATERIALS AND
methodsEight human GBM cell lines were screened for radiosensitivity to the small-molecule c-Met inhibitor MP470 with colony-count assays. Double-strand (ds) DNA breaks was quantified by using antibodies to gamma H2AX. Western blotting demonstrate expression of RAD51, glycogen synthase kinase (GSK)-3beta, and other proteins. A murine xenograft tumor flank model was used for in vivo radiosensitization studies.
resultsMP470 reduced c-Met phosphorylation and enhanced radiation-induced cell kill by 0.4 logs in SF767 cells. Cells pretreated with MP470 had more ds DNA damage than cells treated with radiation alone. Mechanistically, MP470 was shown to inhibit dsDNA break repair and increase apoptosis. MP470 influences various survival and DNA repair related proteins such as pAKT, RAD51 and GSK3beta. In vivo, the addition of MP470 to radiation resulted in a tumor-growth-delay enhancement ratio of 2.9 over radiation alone and extended survival time.
conclusionsGBM is a disease site where radiation is often used to address both macroscopic and microscopic disease. Despite attempts at dose escalation outcomes remain poor. MP470, a potent small-molecule tyrosine kinase inhibitor of c-Met, radiosensitized several GBM cell lines both in vitro and in vivo, and may help to improve outcomes for patients with GBM.
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