ArticleBritish journal of cancer2015
Effects of preset sequential administrations of sunitinib and everolimus on tumour differentiation in Caki-1 renal cell carcinoma.
Article in British journal of cancer, 2015. 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, 18 citations in OpenAlex.
- A phase II study of alternating sunitinib and temsirolimus therapy in patients with metastatic renal cell carcinoma.Cancer medicine · 2023Trial
- TCOF1 affects Golgi secretory pathway contributing to the angiogenesis in renal cancer.Cell communication and signaling : CCS · 2026Article
- Nc886 promotes renal cancer cell drug-resistance by enhancing EMT through Rock2 phosphorylation-mediated β-catenin nuclear translocation.Cell cycle (Georgetown, Tex.) · 2022Article
- Choosing The Right Animal Model for Renal Cancer Research.Translational oncology · 2020Review
- Everolimus inhibits the proliferation and migration of epidermal growth factor receptor-resistant lung cancer cells A549 via regulating the microRNA-4328/phosphatase and tensin homolog signaling pathway.Oncology letters · 2019Article
- Moving Synergistically Acting Drug Combinations to the Clinic by Comparing Sequential versus Simultaneous Drug Administrations.Molecular pharmacology · 2018Article
- Acquired tumor cell resistance to sunitinib by increased invasion and epithelial-mesenchymal transition in LL/2 murine lung cancer.Oncotarget · 2017Article
- Prognostic significance and function of mammalian target of rapamycin in tongue squamous cell carcinoma.Scientific reports · 2017Article
- Time-Based Switching Control of Genetic Regulatory Networks: Toward Sequential Drug Intake for Cancer Therapy.Cancer informatics · 2017Article
- Choosing the right cell line for renal cell cancer research.Molecular cancer · 2016Review
- Isolation and characterization of renal cancer stem cells from patient-derived xenografts.Oncotarget · 2016Article
- In vitro and in vivo efficacy of afatinib as a single agent or in combination with gemcitabine for the treatment of nasopharyngeal carcinoma.Drug design, development and therapy · 2016Article
- Unconventional Functions of Mitotic Kinases in Kidney Tumorigenesis.Frontiers in oncology · 2015Review
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSunitinib (VEGFR/PDGFR inhibitor) and everolimus (mTOR inhibitor) are both approved for advanced renal cell carcinoma (RCC) as first-line and second-line therapy, respectively. In the clinics, sunitinib treatment is limited by the emergence of acquired resistance, leading to a switch to second-line treatment at progression, often based on everolimus. No data have been yet generated on programmed alternating sequential strategies combining alternative use of sunitinib and everolimus before progression. Such strategy is expected to delay the emergence of acquired resistance and improve tumour control. The aim of our study was to assess the changes in tumours induced by three different sequences administration of sunitinib and everolimus.
methodsIn human Caki-1 RCC xenograft model, sunitinib was alternated with everolimus every week, every 2 weeks, or every 3 weeks. Effects on necrosis, hypoxia, angiogenesis, and EMT status were assessed by immunohisochemistry and immunofluorescence.
resultsSunitinib and everolimus programmed sequential regimens before progression yielded longer median time to tumour progression than sunitinib and everolimus monotherapies. In each group of treatment, tumour growth control was associated with inhibition of mTOR pathway and changes from a mesenchymal towards an epithelial phenotype, with a decrease in vimentin and an increase in E-cadherin expression. The sequential combinations of these two agents in a RCC mouse clinical trial induced antiangiogenic effects, leading to tumour necrosis.
conclusionsIn summary, our study showed that alternate sequence of sunitinib and everolimus mitigated the development of mesenchymal phenotype compared with sunitinib as single agent.
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