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| |  High Number of Circulating Endothelial Progenitor Cells Indicates Response to Antiangiogenic Therapy: Presented at AACR By Sophie Bainbridge SAN DIEGO -- April 21, 2008 -- Patients with renal cell carcinoma who are treated with the multikinase inhibitor sunitinib show a significant increase in circulating endothelial progenitor cells, but only if they are responding to treatment, a researcher reported here at the American Society for Cancer Research (AACR) Annual Meeting 2008. Investigator Laura Vroling, a PhD candidate, Vrije University Medical Centre, Amsterdam, Netherlands, presented the findings here on April 15. The number of circulating cells in plasma increased from a median of 82 cells/mL before treatment with sunitinib to 188 cells/mL after 2 weeks of treatment among 18 patients who responded to the drug (P = .001). However, no significant increase emerged in the 5 patients who did not respond to treatment, in whom circulating cells went from a median of 69 cells/mL to 145 cells/mL, (P = .686), Vroling said. In particular, endothelial cells that indicated response to treatment were those that bore the following markers: CD45neg, CD34brignt, and CD133neg. "Our work provides novel data on a potential biomarker for the monitoring of antiangiogenic drug activity in cancer patients as well as identifies a cell type that is a potential target for these agents," said Vroling in an interview. Vroling and colleagues studied the effects of sunitinib therapy on circulating endothelial progenitor cells that contained the markers CD45neg, CD34bright, and CD133neg. They also monitored plasma levels of vascular endothelial growth factor (VEGF), and assessed tumour response according to Response Evaluation Criteria in Solid Tumours. During the 4 weeks of treatment with sunitinib, the number of circulating endothelial progenitor cells increased, and they decreased during a 2-week off-treatment period. VEGF levels also increased during treatment and decreased during the off-treatment period, she said. The researchers also evaluated responses of monocyte and haematopoietic progenitor cells, and found that these cells demonstrated the opposite pattern, decreasing during treatment and increasing when treatment was stopped. "Our research suggests that circulating endothelial progenitor cells are increased in cancer patients responding to antiangiogenic therapy with sunitinib in a treatment-specific way, but this effect does not appear to be related to plasma VEGF levels," Vroling said. She added that the role of circulating endothelial progenitor cells in human tumour angiogenesis, and their potential for predicting treatment outcome of anti-VEGF therapy, needs to be explored further in larger, clinical trials. "Our ultimate aim is to be able to determine in advance -- before the patient gets treatment -- if he or she will benefit. We would want to see their response, based on the first 2 weeks of treatment, in terms of their rise in circulating endothelial progenitor cells," she concluded in an interview.
[Presentation title: CD34bright/CD133neg Candidate Circulating Endothelial Progenitor Cells (Ccepcs) Are a Potential Biomarker During Treatment With Sunitinib or Bevacizumab. Abstract 4956]
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