Vascular-disrupting agents (VDA): mechanism of action and anti-tumor activity

Despite more than 50 years of anti-cancer studies, most cancer patients are still being treated with chemotherapeutics that not only kill cancer cells but also healthy, rapidly proliferating cells throughout the body. Thus, there is an urgent need to develop novel therapeutic agents with improved efficacy and tolerance. As such, Vascular Disrupting Agents (VDAs) have been used in anti-cancer therapy as a viable strategy. They cause direct damage to the already established tumor endothelium, leading to tumor necrosis. Unfortunately, VDAs always leave a residual viable rim, which is the reason for tumor recurrence and metastasis.

In collaboration with the medicinal chemistry groups of prof. Pérez-Pérez (Spain), Hansen (Norway) and Dehaen (KU Leuven) we have recently identified novel VDAs that cause microtubule depolymerization and tumor cell apoptosis. Here we are focusing on studying the mechanism of action of these compounds, developing compound prodrugs, and evaluating their antitumor activity in various mouse models in combination with other therapeutic strategies (including anti-angiogenic agents and chemotherapy), in order to improve their effectiveness.