Abnormalization of Tumor Vessels to Improve the Efficacy of Chemotherapy

Achieving an adequate drug concentration at the tumor site is a major challenge in systemic therapy. Besides massive dilution in the blood and uptake by other organs, the pathophysiology of the tumor hampers drug uptake. Vasoactive compounds, like tumor necrosis factor-alpha (TNF) or Cilengitide manipulates the tumor-associated vasculature improving the permeability of these vessels. In this process, we have called tumor vessel abnormalization, the co-administered chemotherapeutic drug, melphalan or liposomal doxorubicin (Doxil), can traverse more easily from the blood circulation into the surrounding tumor tissue. This increased intratumoral drug accumulation ultimately results in an improved tumor response.