ABSTRACT
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In recent years, there has been significant progress in the clinical development of antiangio-
genic 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 circu-
lating 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.
