ArticleOncology reports2013
A novel c-Met inhibitor, MK8033, synergizes with carboplatin plus paclitaxel to inhibit ovarian cancer cell growth.
Article in Oncology reports, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 26 citations in OpenAlex.
- Mechanistic insights into c-Met rs368750834 mutation and a bifunctional CAR-T strategy for serous ovarian carcinoma.Journal of ovarian research · 2025Article
- E2F1-Associated Purine Synthesis Pathway Is a Major Component of the MET-DNA Damage Response Network.Cancer research communications · 2024Article
- Review the progression of ovarian clear cell carcinoma from the perspective of genomics and epigenomics.Frontiers in genetics · 2023Review
- Combined Expression of HGFR with Her2/neu, EGFR, IGF1R, Mucin-1 and Integrin α2β1 Is Associated with Aggressive Epithelial Ovarian Cancer.Biomedicines · 2022Article
- The role of MET in chemotherapy resistance.Oncogene · 2021Review
- First-in-human phase I dose escalation study of MK-8033 in patients with advanced solid tumors.Investigational new drugs · 2018Article
- Prognostic impact of high c-Met expression in ovarian cancer: a meta-analysis.Journal of Cancer · 2018Article
- Dasatinib + Gefitinib, a non platinum-based combination with enhanced growth inhibitory, anti-migratory and anti-invasive potency against human ovarian cancer cells.Journal of ovarian research · 2017Article
- c-MET as a Potential Therapeutic Target in Ovarian Clear Cell Carcinoma.Scientific reports · 2016Article
- Monitoring of ovarian cancer cell invasion in real time with frequency-dependent impedance measurement.American journal of physiology. Cell physiology · 2016Article
- Ockham's razor for the MET-driven invasive growth linking idiopathic pulmonary fibrosis and cancer.Journal of translational medicine · 2016Review
- MicroRNA-224 promotes the sensitivity of osteosarcoma cells to cisplatin by targeting Rac1.Journal of cellular and molecular medicine · 2016Article
- The Therapeutic Potential of Targeting the HGF/cMET Axis in Ovarian Cancer.Molecular diagnosis & therapy · 2016Review
- Small molecule inhibitor of c-Met (PHA665752) suppresses the growth of ovarian cancer cells and reverses cisplatin resistance.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Molecular Subtyping of Serous Ovarian Cancer Based on Multi-omics Data.Scientific reports · 2016Article
- Dynamic modulation of phosphoprotein expression in ovarian cancer xenograft models.BMC cancer · 2016Article
- INC280, an orally available small molecule inhibitor of c-MET, reduces migration and adhesion in ovarian cancer cell models.Scientific reports · 2015Article
- Sorafenib and DE605, a novel c-Met inhibitor, synergistically suppress hepatocellular carcinoma.Oncotarget · 2015Article
- cMET in NSCLC: Can We Cut off the Head of the Hydra? From the Pathway to the Resistance.Cancers · 2015Review
- HGF/c-MET Axis in Tumor Microenvironment and Metastasis Formation.Biomedicines · 2015Review
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
Abstract
Elevated serum levels of hepatocyte growth factor (HGF) and high tumor expression of c-Met are both indicators of poor overall survival from ovarian cancer (OVCA). In the present study, we evaluated the role of the HGF signaling pathway in OVCA cell line chemoresistance and OVCA patient overall survival as well as the influence of HGF/c-Met signaling inhibition on the sensitivity of OVCA cells to combinational carboplatin plus paclitaxel therapy. The prevalence of the HGF receptor, c-Met, was determined by immunohistochemistry in primary OVCA samples (n=79) and OVCA cell lines (n=41). The influence of the c-Met-specific inhibitor MK8033 on OVCA cell sensitivity to combinations of carboplatin plus paclitaxel was examined in a subset of OVCA cells (n=8) by CellTiter-Blue cell viability assays. Correlation tests were used to identify genes associated with response to MK8033 and carboplatin plus paclitaxel. Identified genes were evaluated for influence on overall survival from OVCA using principal component analysis (PCA) modeling in an independent clinical OVCA dataset (n=218). Immunohistochemistry analysis indicated that 83% of OVCA cells and 92% of primary OVCA expressed the HGF receptor, c-Met. MK8033 exhibited significant anti-proliferative effects against a panel of human OVCA cell lines. Combination index values determined by the Chou-Talalay isobologram equation indicated synergistic activity in combinations of MK8033 and carboplatin plus paclitaxel. Pearson's correlation identified a 47-gene signature to be associated with MK8033-carboplatin plus paclitaxel response. PCA modeling indicated an association of this 47-gene response signature with overall survival from OVCA (P=0.013). These data indicate that HGF/c-Met pathway signaling may influence OVCA chemosensitivity and overall patient survival. Furthermore, HGF/c-Met inhibition by MK8033 represents a promising new therapeutic avenue to increase OVCA sensitivity to carboplatin plus paclitaxel.
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