Anti-VEGF-induced hypertension and cancer outcomes: translating research into clinical practice

The vascular endothelial growth factor (VEGF) physiologically
regulates angiogenesis and maintains vascular homeostasis
in vitro and in vivo. The two main receptors mediating
the effects of VEGF are the structurally related tyrosine kinases,
VEGFR1 (Flt-1) and VEGFR2 (Flk-1). However, alterations in
VEGF expression and signaling play an important role in cancer
angiogenesis and progression in several types of cancer. Nitric oxide (NO), a key endogenous modulator of vascular
homeostasis, has been shown to mediate the main physiological
and pathophysiological effects of VEGF, mainly through
activation of VEGFR2. Over the last decade, an increasing
number of drugs inhibiting the effects of VEGF (anti-VEGF
drugs) have been introduced in clinical practice for the management
of patients with cancer and eye disease conditions. The use of anti-VEGF drugs for these indications is based
on their ability to inhibit excessive and/or inappropriate angiogenesis
either locally (e.g. in the eye) or systemically, thereby
slowing disease progression. In cancer, systemic inhibition
of angiogenesis primarily involves inhibition of the binding
of systemic VEGF to both VEGFR1 and VEGFR2, either by
targeting circulating VEGF or its receptors.