Therapeutic Targeting of the Tumor Vasculature: Past, Present and Future
Pp. 1-29 (29)
Peace Mabeta, Mike Sathekge and Vanessa Steenkamp
Tumor progression relies on a constant supply of oxygen and nutrients.
Angiogenesis, the formation of neovessel from existing microvessels, is a prerequisite
for the growth of many tumors. Significant advances have been made in delineating the
interplay between pro- and anti-angiogenic factors that foster an environment that
promotes the angiogenic phenotype in tumors. Of these angiogenic regulators, vascular
endothelial growth factor-A (VEGF-A) and its cognate receptor, vascular endothelial
growth factor receptor-2 (VEGFR-2) have been the most studied.
Various angiogenesis inhibitors (AIs) that target VEGF-A and VEGFR-2 have been
developed for use as monotherapy or as part of combination therapies with standard
chemotherapy. However, these AIs have thus far produced modest results, in part
owing to compensatory pathways that have led to disease refractory.
To overcome refractory to disease, normalization of the tumor vasculature and
broadening of the scope of therapeutic targeting are necessary. Furthermore, predictive
biomarkers can enhance efficacy by enabling the early detection of resistance as well as
the determination of clinical benefit. Herein, the therapeutic approaches that target
multiple pathways and components of the tumor microenvironment, as well as those
that normalize the vasculature are explored. In addition, the future application of noninvasive
imaging to monitor the effects of AIs on the tumor vessels is discussed.
Angiogenesis, Bevacizumab, Cancer, Imaging, Immunotherapy,
Hypoxia, Vascular endothelial growth factor.
Department of Physiology, University of Pretoria, Pretoria, South Africa.