Soluble isoforms of vascular endothelial growth factor are predictors of response to sunitinib in metastatic renal cell carcinomas.Report as inadecuate

Soluble isoforms of vascular endothelial growth factor are predictors of response to sunitinib in metastatic renal cell carcinomas. - Download this document for free, or read online. Document in PDF available to download.

* Corresponding author 1 Hématologie -Immunologie -Cibles thérapeutiques 2 IMRB - Institut Mondor de recherche biomédicale 3 Biostatistique et épidemiologie clinique 4 CeRePP National Group - Service d-urologie 5 Laboratoire de pharmacologie 6 CRRET - Laboratoire de recherche sur la croissance cellulaire, la réparation et la régénération tissulaires 7 Bases Moleculaires de l-Homeostasie Cutanee : Inflammation, Reparation et Cancer 8 Cibles Moleculaires Dans les Cancers

Abstract : BACKGROUND: Angiogenesis is the target of several agents in the treatment of malignancies, including renal cell carcinoma RCC. There is a real need for surrogate biomarkers that can predict selection of patients who may benefit from antiangiogenic therapies, prediction of disease outcome and which may improve the knowledge regarding mechanism of action of these treatments. Tyrosine kinase inhibitors TKI have proven efficacy in metastatic RCC mRCC. However, the molecular mechanisms underlying the clinical response to these drugs remain unclear. METHODOLOGY-PRINCIPAL FINDINGS: The present study aimed to identify molecular biomarkers associated with the response to sunitinib, a Tyrosine kinase inhibitor. To evaluate this relationship, primary tumors from 23 metastatic RCC patients treated by sunitinib were analyzed for a panel of 16 biomarkers involved in tumor pathways targeted by sunitinib, using real-time quantitative reverse-transcriptase PCR. Nine of the 23 patients 39% responded to sunitinib. Among transcripts analyzed, only the levels of vascular endothelial growth factor VEGF soluble isoforms VEGF121 and VEGF165 were associated with the response to sunitinib P = 0.04 for both. Furthermore, the ratio of VEGF soluble isoforms VEGF121-VEGF165 was significantly associated with prognosis P = 0.02. CONCLUSIONS: This preliminary study provides a promising tool that might help in the management of metastatic RCC, and could be extended to other tumors treated by TKI.

Author: Bernard Paule - Laurence Bastien - Emmanuelle Deslandes - Olivier Cussenot - Marie-Pierre Podgorniak - Yves Allory - Benyoussef N



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