ArticleOncotarget2017
The selective MEK1 inhibitor Selumetinib enhances the antitumor activity of everolimus against renal cell carcinoma in vitro and in vivo.
Article in Oncotarget, 2017. 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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Who cites it
13 citing papers in PubMed, 19 citations in OpenAlex.
- Clinical value and mechanism of CDKN2A in clear cell renal cell carcinoma.Discover oncology · 2025Article
- Inhibitory effects of the combination of rapamycin with gemcitabine plus paclitaxel on the growth of pancreatic cancer tumors.Human cell · 2025Article
- Machine learning-driven prognostic analysis of cuproptosis and disulfidptosis-related lncRNAs in clear cell renal cell carcinoma: a step towards precision oncology.European journal of medical research · 2024Article
- Combining the Tyrosine Kinase Inhibitor Cabozantinib and the mTORC1/2 Inhibitor Sapanisertib Blocks ERK Pathway Activity and Suppresses Tumor Growth in Renal Cell Carcinoma.Cancer research · 2023Article
- Article
- MAPK inhibitor sensitivity scores predict sensitivity driven by the immune infiltration in pediatric low-grade gliomas.Nature communications · 2023Article
- Integrated bioinformatic analysis and cell line experiments reveal the significant role of the novel immune checkpoint TIGIT in kidney renal clear cell carcinoma.Frontiers in oncology · 2023Article
- Article
- ERK Inhibitor Enhances Everolimus Efficacy through the Attenuation of dNTP Pools in Renal Cell Carcinoma.Molecular therapy. Nucleic acids · 2019Article
- CIC protein instability contributes to tumorigenesis in glioblastoma.Nature communications · 2019Article
- Ribonucleotide reductase subunit M2 as a novel target for clear-cell renal cell carcinoma.OncoTargets and therapy · 2019Article
- Dual-Inhibition of mTOR and Bcl-2 Enhances the Anti-tumor Effect of Everolimus against Renal Cell CarcinomaJournal of Cancer · 2019Article
- Attenuation of everolimus-induced cytotoxicity by a protective autophagic pathway involving ERK activation in renal cell carcinoma cells.Drug design, development and therapy · 2018Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Renal cell carcinoma (RCC) is a urologic malignant cancer and often diagnosed at an advanced stage, which results in high mortality. Targeted therapy may improve the quality of life and survival of patients who are not suitable for nephrectomy. Everolimus, an mTOR inhibitor, is currently used as sequential or second-line therapy for RCC refractory to Sunitinib or sorafenib. However, its efficiency is palliative. In this study, we evaluated whether the antitumor activity of everolimus against RCC is enhanced by Selumetinib, a selective MEK1 inhibitor. We discovered that everolimus in combination with Selumetinib synergistically inhibited the proliferation of Caki-1, 786-O and 769-P cells in vitro. Mechanistically, this combination decreased p-RPS6 and p-4E-BP1 dramatically, which causes G1 cell cycle arrest and prevents reactivation of AKT and ERK. In vivo, the antitumor efficacy and pharmacodynamic biomarkers of the combination therapy were recapitulated in Caki-1 xenograft model. In addition, this combination treatment potently inhibited angiogenesis in xenograft models by impairing VEGF secretion from tumor cells. Our findings provide a sound evidence that combination of everolimus and Selumetinib is a potential dual-targeted strategy for renal cell carcinoma.
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