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Differentiation and Definition of Vascular-Targeted Therapies

¹ University of Florida, Gainesville, Florida; ² University of Bradford, Bradford, West Yorkshire, United Kingdom; ³ University of Newcastle upon Tyne, United Kingdom; ⁴ Thomas Jefferson University, Philadelphia, Pennsylvania; ⁵ Erasmus Medical Centre, Rotterdam, the Netherlands; ⁶ Aarhus University Hospital, Aarhus, Denmark; ⁷ Tumor Biology Center, Freiburg, Germany; and ⁸ Karmanos Cancer Institute, Southfield, Michigan

Requests for reprints: Dietmar W. Siemann, Department of Radiation Oncology, University of Florida, P.O. Box 100385, Gainesville, FL 32610. Phone: 352-265-0287; Fax: 352-265-0759; E-mail: siemadw{at}ufl.edu.

The therapeutic potential of targeting the tumor vascular supply is now widely recognized. Intense research and development activity has resulted in a variety of investigational agents, a number of which are currently in clinical development. As these novel agents are quite distinct from the cytotoxic drugs conventionally used in the treatment of solid tumors, it will be particularly important to ensure early differentiation of these vascular-targeted therapies in order to encourage widespread understanding of their potential benefits and application in the clinic. Two distinct groups of vascular-targeted therapies have evolved: antiangiogenic agents and vascular-disrupting approaches. These differ in three key respects: their physiologic target, the type or extent of disease that is likely to be susceptible, and the treatment scheduling. Inhibitors of angiogenesis interfere with new vessel formation and therefore have a preventative action, require chronic administration, and are likely to be of particular benefit in early-stage or asymptomatic metastatic disease. Vascular-disrupting agents target the established tumor blood vessels, resulting in tumor ischemia and necrosis. These agents are therefore given acutely, show more immediate effects, and may have particular efficacy against advanced disease. It is essential that these agents can be readily distinguished from conventional therapies and that an understanding of key differences between the two types of vascular-targeted therapies is fostered. Here, a simple taxonomy and nomenclature is proposed in anticipation that the therapeutic potential of this novel class can be realized as these approaches advance in clinical settings and a new anticancer strategy becomes available in the clinic.

Key Words: vascular targeting • antiangiogenic therapies • vascular disruptive agents

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