e13508 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. The present study aimed to identify molecular biomarkers associated with the response to sunitinib, a TKI. Methods: To evaluate this relationship, primary tumors from 23 clear-cell 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. Results: Eighteen of the 23 patients (78%) responded to sunitinib (9 responses and 9 stabilizations). Among transcripts analyzed, only the levels of vascular endothelial growth factor (VEGF) soluble isoforms (VEGF121 and VEGF165) were associated with the response to sunitinib. Indeed, the tumor transcript levels were significantly higher in responding patients compared with patients who had a failure to treatment: median 1222 versus 241 for VEGF121 (p = 0.04), and median 905 versus 352 for VEGF165 (p = 0.04). For tumors overexpressing VEGF121 and VEGF165, the probability of response was 81% and 90%, respectively. Furthermore, the ratio of VEGF soluble isoforms (VEGF121/VEGF165) was significantly associated with prognosis. Indeed, the overall survival of patients with a ratio lower than 1.25 (cut-off value determined from the third quartile) was significantly higher than those of patients with a ratio higher than 1.25 (p = 0.02; median survival time not reached, versus 25.2 months). 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. No significant financial relationships to disclose.