Abstract: Blocking tumor growth by targeting the tumor vasculature is a promising approach in cancer therapy. Both, disrupting
tumor vessels as well as normalization of tumor vessel abnormalities have shown anti-cancer efficacy. A plethora
of agents that act on the tumor vasculature have been developed; however, so far few have shown clinical benefits.
Among the successful agents, inhibitors of the mammalian target of rapamycin (mTOR) are able to reduce tumor growth
by targeting tumor vessels. mTOR inhibition exerts at least three different effects on the tumor vasculature. First, it reduces
tumor angiogenesis. Second it normalizes the tumor vasculature and third, it promotes the formation of thrombosis
in tumor vessels. The characterization of the molecular functions regulated by mTOR and of relevance to the tumor vasculature
is therefore important in order to further identify biological mechanisms involved in the tumor vascular network as
well as to improve the efficacy of these inhibitors. Here, we will first enumerate the evidences for the anti-angiogenic activities
of mTOR inhibitors and describe the molecular mechanisms involved. We will further analyze the effects of
mTOR inhibition on vascular normalization and also describe how mTOR inhibition promotes thrombosis formation specifically
in tumor vessels. Finally, we will describe a new generation of mTOR inhibitors and examine their effects on the
tumor vasculature