Effects of preset sequential administrations of sunitinib and everolimus on tumour differentiation in Caki-1 renal cell carcinoma.

Details

Ressource 1Download: 25422908_BIB_F66A07ED9ED7.pdf (2424.30 [Ko])
State: Public
Version: Final published version
Serval ID
serval:BIB_F66A07ED9ED7
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Effects of preset sequential administrations of sunitinib and everolimus on tumour differentiation in Caki-1 renal cell carcinoma.
Journal
British Journal of Cancer
Author(s)
Dos Santos C., Tijeras-Raballand A., Serova M., Sebbagh S., Slimane K., Faivre S., de Gramont A., Raymond E.
ISSN
1532-1827 (Electronic)
ISSN-L
0007-0920
Publication state
Published
Issued date
2015
Peer-reviewed
Oui
Volume
112
Number
1
Pages
86-94
Language
english
Notes
Publication types: Journal Article
Abstract
BACKGROUND: Sunitinib (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.
METHODS: In 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.
RESULTS: Sunitinib 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.
CONCLUSIONS: In summary, our study showed that alternate sequence of sunitinib and everolimus mitigated the development of mesenchymal phenotype compared with sunitinib as single agent.
Pubmed
Web of science
Open Access
Yes
Create date
11/02/2015 12:18
Last modification date
20/08/2019 16:22
Usage data