VEGF Signaling Inhibitors as Biomarkers

A systematic review using PubMed, MEDLINE and American Society of Clinical Oncologist (ASCO) databases was conducted for articles (including abstracts) presented in 2007-2009 to compare undertaken new small-molecule tyrosine kinase inhibitors with VEGF receptor as one of their targets (Wood et al. 2009). Factors considered included mode of action (targets), toxicity and usefulness of biomarker data. Search terms included ‘angiogenesis inhibitors’, ‘tyrosine kinase inhibitors’, ‘VEGF’ and ‘biomarkers’. Nine compounds were selected for detailed comparison. The toxicity profiles of the compounds were similar. Many exposure biomarkers were identified that helped to determine the dose and scheduling of these compounds in clinical trials. Progress has also been made in identifying potential efficacy and predictive biomarkers for these new agents; however, these are yet to be validated.

VEGF-PET Imaging for Analysis of Angiogenic Changes within a Tumor

Non-invasive imaging of angiogenesis could ease the optimization of antiangiogenesis treatments for cancer. A study has evaluated the role of VEGF-PET as a biomarker of dynamic angiogenic changes in tumors following treatment with the kinase inhibitor sunitinib (Nagengast et al. 2010). The effects of sunitinib treatment and withdrawal on the tumor was investigated using the new VEGF-PET tracer ⁸⁹Zr-ranibizumab as well as ¹⁸F-FDG PET, and ¹⁵O-water PET in mouse xenograft models of human cancer. The imaging results were compared with tumor growth, VEGF plasma levels and immunohistologic analyzes. In contrast to ¹⁸F-FDG and ¹⁵O-water PET, VEGF-PET demonstrated dynamic changes during sunitinib treatment within the tumor with a strong decline in signal in the tumor center and only minimal reduction in tumor rim, with a pronounced rebound after sunitinib discontinuation. VEGF-PET results corresponded with tumor growth and immunohisto- chemical vascular- and tumor- biomarkers. These findings highlight the strengths of VEGF-PET imaging to enable serial analysis of angiogenic changes in different areas within a tumor.