Dutch scientists have identified two potential biomarkers that will allow doctors to gauge the effectiveness of two drugs given for kidney, and non-small cell lung cancer.
"Our work provides novel data on a potential biomarker for the monitoring of anti-angiogenic drug activity in cancer patients, as well as identifies a cell type that is a potential target for these agents," said Laura Vroling, a researcher in the Department of Medical Oncology, VU University Medical Center, Amsterdam.
AdvertisementIt is known that the vascular endothelial growth factor (VEGF) receptor is known to target agents bevacizumab and sunitinib are effective against several cancers-like non-small cell lung cancer, colorectal and kidney cancer. However, it has been unclear as to which subset of patients will benefit most from such agents.
"Therefore, it is of great importance to identify and validate biomarkers for early response or duration of response," Vroling said.
During the study, the researchers studied therapy-induced changes in circulating endothelial progenitor cells (ccEPCs) characterized by the markers CD45neg, CD34bright and CD133neg during sunitinib or bevacizumab treatment.
The study included 23 patients with renal cell cancer, and 19 with non-small cell lung cancer.
The researchers also monitored plasma levels of VEGF, and assessed tumour response with computed tomography scans according to the RECIST criteria.
"This is the first study to assess the kinetics of ccEPCs together with other circulating cells in the peripheral blood of patients with renal cell cancer during the first cycle of sunitinib treatment," Vroling said.
The research team observed that the ccEPC increases paralleled the rise in plasma VEGF levels during a four-week "on" period of treatment with sunitinib, while they decreased during the two-week "off" period.
Vroling noted that monocytes and hematopoietic progenitor cells (HPCs) demonstrated the opposite pattern.
"In a preliminary analysis, we found a significant difference in the change of ccEPC numbers and VEGF levels after two weeks of treatment between patients with clinical benefit and progressive disease. We also noted that an increase of ccEPCs was indicative of a longer progression-free survival in this small group of patients," Vroling said.
The researchers also observed that in patients with non-small cell lung cancer treated with bevacizumab and erlotinib, ccEPC levels increased, while free plasma VEGF levels decreased.
Vroling revealed that ccEPC levels did not rise in a control group treated with erlotinib alone.
"These data suggest that ccEPCs are increased in cancer patients in an anti-angiogenic, treatment-specific way," she said.
Vroling further said that that effect did not seem to be related to plasma VEGF levels.
"In our study for the first time the behavior of two CD34bright cell populations, (CD45neg) candidate cEPCs and (CD45dim) HPCs were monitored and showed a different response of both cell populations during sunitinib or bevacizumab therapy. The role of ccEPCs in human tumour angiogenesis and their potential in prediction of treatment outcome of anti-VEGF therapy needs to be addressed in future, larger clinical cohorts," she said.