The tumour vasculature in metastatic CRC: Beyond the obvious


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Lee Ellis1
1MD Anderson Cancer Center, Houston, Texas, USA

Abstract

Despite a great deal of publicity regarding anti-angiogenic therapies (more specifically, VEGF-targeted therapies), results in the clinic vary a great deal among tumor types and even stage of disease. In patients with metastatic colorectal cancer, despite the initial promise of the addition of VEGF-targeted agents to standard cytotoxic regimens, the benefit of such therapy has come under scrutiny. Although numerous theories have been proposed for the mechanisms of action of VEGF-targeted agents, we must recognize that one cannot apply a single mechanism to all tumor types. Indeed, anti-VEGF therapy may have multiple effects as an antineoplastic agent including effects on the vasculature, the host immune cells, and even direct effects on tumour cells. If we knew the exact mechanism of action of VEGF-targeted agents, finding predictive biomarkers would be easy. However, despite an intensive search for biomarkers of efficacy for VEGF-targeted therapies, none have been identified, again demonstrating the complexity of the biology of VEGF and the tumor vasculature. Our laboratory has studied the tumor vasculature of CRCs for nearly 2 decades and recently we found that endothelial cells can exert a profound effect on tumor cell survival that is independent of blood flow. This presentation will discuss the role of “angiocrine” signaling in the tumor vascular bed in CRC, providing the opportunity for discovery of new vascular derived targets for therapeutic intervention.