Title:New Vascular Disrupting Agents in Upper Gastrointestinal Malignancies
Volume: 21
Issue: 8
Author(s): A.E. Quatrale, L. Porcelli, A. Gnoni, G. Numico, A. Paradiso and A. Azzariti
Affiliation:
Keywords:
Gastrointestinal cancers, upper gastrointestinal malignancies, vascular disrupting agents.
Abstract: Antivascular approaches aim to cause rapid and catastrophic shutdown in the vascular function of the tumour,
leading to extensive tumour cell death. Tumour vascular disrupting agents (VDAs) are a new class of cancer therapies that
target the existing vasculature of tumours, taking advantage of the relative instability of tumour vasculature and its supporting
structures. Treatment with VDAs induces a rapid collapse and regression of tumour vessels, with a consequent
deprivation of blood and oxygen which leads to ischemic or hemorrhagic necrosis of the tumour. In this review, an overview
of the most recently developed vascular disrupting agents is reported, focusing on the biological effects exerted by
these compounds on endothelial cells and tumour vasculature, potentially effective in the treatment of several malignancies
including upper gastrointestinal tumours. In particular, we have focused on the antimitotic agent combretastatin and
its numerous synthetic analogues such as combretastatin A-4-phosphate, OXI4503, and AVE8062, and on the colchicine
analogue ZD6126.
