Blood-based biomarkers for VEGF inhibitors

In recent years, there has been significant progress in the clinical development of antiangiogenic therapy, particularly inhibitors of the VEGF pathway. Despite this progress, however, the biological activity of these agents remains difficult to assess because they do not typically lead to objective responses as judged by tumor shrinkage when used as monotherapy. Furthermore, we do not yet have validated methods for identifying which patients are most likely to respond to treatment, selecting the optimal dose, or determining whether the intended molecular target has been effectively inhibited. Ideally such methods should be noninvasive and practical for routine clinical care. In this chapter we review blood-based biomarkers currently under investigation for VEGF pathway inhibitors. These include circulating proangiogenic factors and receptors (i.e., soluble VEGFR-1 and VEGFR-2); markers of hypoxia and endothelial damage; and cellular populations in the peripheral blood such as circulating endothelial cells (CECs). Several of these markers are promising but further preclinical and clinical studies will be needed to determine their potential utility in the clinical setting.