Circulating endothelial cells are an early predictor in renal cell carcinoma for tumor response to sunitinib

Analyses of CEC, monocytes, and sVEGFR-2 were accomplished for twenty-six consecutive patients with metastatic RCC who received treatment with sunitinib (50 mg, 4 wks on 2 wks off schedule) at our institution in 2005 and 2006.In RCC patients CEC are elevated to 49 ± 44/ml (control 8 ± 8/ml; P = 0.0001). Treatment with sunitinib is associated with an increase in CEC within 28 days of treatment in patients with a Progression free survival (PFS) above the median to 111 ± 61 (P = 0.0109), whereas changes in patients with a PFS below the median remain insignificant 69 ± 61/ml (P = 0.1848). Monocytes and sVEGFR2 are frequently altered upon sunitinib treatment, but fail to correlate with clinical response, defined by PFS above or below the median.Sunitinib treatment is associated with an early increase of CEC in responding patients, suggesting superior endothelial cell damage in these patients as a putative predictive biomarker.Tyrosine kinase inhibitors (TKI) were recently successfully added to the armentarium to treat renal cell carcinoma (RCC). Sunitinib, a first generation TKI which targets VEGFR1-3, PDGFR α/？, KIT, RET, CSF 1R and FLT-3, has recently been approved for the treatment of RCC [1]. Its antitumor activity is at least partially mediated through inhibition of tumor vessel formation, which can be demonstrated through sophisticated imaging techniques, such as dynamic contrast enhanced MRI. As these techniques are not commonly available to most physicians, biomarkers which predict biological and antitumor activity are desperately needed to adequately monitor tumor therapy and predict tumor response to sunitinib.In RCC, inhibition of vessel formation is thought to be the prime mechanism to achieve antitumor activity [2]. The biological relevance of the different VEGFR family members in this process was elucidated in murine models, and VEGFR-2 was determined to be the main regulator of neo-angiogenesis and the most promising target for therapeutic intervention [3]