ArticleJournal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer2012
C-Met inhibitor MK-8003 radiosensitizes c-Met-expressing non-small-cell lung cancer cells with radiation-induced c-Met-expression.
Article in Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 73 citations in OpenAlex.
- A MET-Targeted Variable New Antigen Receptor (VNAR) Theranostic for Non-Small Cell Lung Cancer.bioRxiv : the preprint server for biology · 2026Article
- Targeting mesenchymal-epithelial transition factor signaling in cancer: from genetic alterations to clinical advances and future prospects.Molecular biology reports · 2025Review
- The anticancer effects of Aronia berry extract are mediated by Chk1 and p53 in colorectal cancer.Phytomedicine : international journal of phytotherapy and phytopharmacology · 2024Article
- E2F1-Associated Purine Synthesis Pathway Is a Major Component of the MET-DNA Damage Response Network.Cancer research communications · 2024Article
- Capmatinib is an effective treatment for MET-fusion driven pediatric high-grade glioma and synergizes with radiotherapy.Molecular cancer · 2024Article
- MET Inhibitor Capmatinib Radiosensitizes MET Exon 14-Mutated and MET-Amplified Non-Small Cell Lung Cancer.International journal of radiation oncology, biology, physics · 2024Article
- MET Inhibitor Capmatinib Radiosensitizes MET Exon 14-Mutated and MET-Amplified Non-Small Cell Lung Cancer.bioRxiv : the preprint server for biology · 2023Article
- CAR T cell-based immunotherapy and radiation therapy: potential, promises and risks.Molecular cancer · 2023Review
- The benefit of co-targeting PARP-1 and c-Met on the efficacy of radiotherapy in wild type BRAF melanoma.Frontiers in medicine · 2023Article
- Development and characterization of patient-derived xenografts from non-small cell lung cancer brain metastases.Scientific reports · 2021Article
- c-Met expression in renal cell carcinoma with bone metastases.Journal of bone oncology · 2020Review
- Review
- Combination therapy with c-met inhibitor and TRAIL enhances apoptosis in dedifferentiated liposarcoma patient-derived cells.BMC cancer · 2019Article
- Innovative Therapeutic Strategies for Effective Treatment of Brain Metastases.International journal of molecular sciences · 2019Review
- Enhancing the Radiation Response in KRAS Mutant Colorectal Cancers Using the c-Met Inhibitor Crizotinib.Translational oncology · 2019Article
- First-in-human phase I dose escalation study of MK-8033 in patients with advanced solid tumors.Investigational new drugs · 2018Article
- Combining immunotherapy with radiation therapy in thoracic oncology.Journal of thoracic disease · 2018Review
- BPI-9016M, a c-Met inhibitor, suppresses tumor cell growth, migration and invasion of lung adenocarcinoma via miR203-DKK1.Theranostics · 2018Article
- Preclinical rationale for combining radiation therapy and immunotherapy beyond checkpoint inhibitors (i.e., CART).Translational lung cancer research · 2017Review
- 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
10 authors at 1 institution in 1 country.
Funding
Abstract
introductionThe radiation doses used to treat unresectable lung cancer are often limited by the proximity of normal tissues. Overexpression of c-Met, a receptor tyrosine kinase, occurs in about half of non-small-cell lung cancers (NSCLCs) and has been associated with resistance to radiation therapy and poor patient survival. We hypothesized that inhibiting c-Met would increase the sensitivity of NSCLC cells to radiation, enhancing the therapeutic ratio, which may potentially translate into improved local control.
methodsWe tested the radiosensitivity of two high-c-Met-expressing NSCLC lines, EBC-1 and H1993, and two low-c-Met-expressing lines, A549 and H460, with and without the small-molecule c-Met inhibitor MK-8033. Proliferation and protein expression were measured with clonogenic survival assays and Western blotting, respectively. γ-H2AX levels were evaluated by immunofluorescence staining.
resultsMK-8033 radiosensitized the high-c-Met-expressing EBC-1 and H1993 cells but not the low-c-Met-expressing cell lines A549 and H460. However, irradiation of A549 and H460 cells increased the expression of c-Met protein at 30 minutes after the irradiation. Subsequent targeting of this up-regulated c-Met by using MK-8033 followed by a second radiation dose reduced the clonogenic survival of both A549 and H460 cells. MK-8033 reduced the levels of radiation-induced phosphorylated (activated) c-Met in A549 cells.
conclusionsThese results suggest that inhibition of c-Met could be an effective strategy to radiosensitize NSCLC tumors with high basal c-Met expression or tumors that acquired resistance to radiation because of up-regulation of c-Met.
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Registered trials
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