Tumor resistance to vascular disrupting agents: mechanisms, imaging, and solutions

// Wenjie Liang 1 , Yicheng Ni 2 and Feng Chen 1 1 Department of Radiology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China 2 Radiology Section, University Hospitals, University of Leuven, Leuven, Belgium Correspondence to: Feng Chen, email: // Keywords : vascular disrupting agents, resistance, imaging, solutions Received : September 27, 2015 Accepted : January 14, 2016 Published : January 24, 2016 Abstract The emergence of vascular disrupting agents (VDAs) is a significant advance in the treatment of solid tumors. VDAs induce rapid and selective shutdown of tumor blood flow resulting in massive necrosis. However, a viable marginal tumor rim always remains after VDA treatment and is a major cause of recurrence. In this review, we discuss the mechanisms involved in the resistance of solid tumors to VDAs. Hypoxia, tumor-associated macrophages, and bone marrow-derived circulating endothelial progenitor cells all may contribute to resistance. Resistance can be monitored using magnetic resonance imaging markers. The various solutions proposed to manage tumor resistance to VDAs emphasize combining these agents with other approaches including antiangiogenic agents, chemotherapy, radiotherapy, radioimmunotherapy, and sequential dual-targeting internal radiotherapy.