Endothelium as a target in the design of novel tumour antiangiogenic / vasculature-targeting agents

Abstract

This thesis begins with a review of tumour growth and development, with a particular focus on angiogenesis. The numerous mechanisms which regulate the process are touched upon, with current and fiiture antiangiogenic agents reviewed. This leads on to a discussion on tumour vasculature targeting agents and their role in chemotherapy, where tubulin binding agents are emphasised. The tumour angiogenesis/vasculature targeting agent, combretastatin A-4 is discussed in detail as are the different derivatives that have been synthesised based on this tubulin inhibitor. This leads onto a discussion on aminopeptidase N (APN), its role in cancer and more specifically in tumour angiogenesis. Finally, the concept of creating a hybrid type inhibitor of tumour angiogenesis/vasculature by incorporating both tubulin binding and APN inhibitory peptidal moieties into a single compound is presented.