Tumor vascular infarction: prospects and challenges

Induction of thrombosis in tumor vasculature represents an appealing strategy for combating cancer. Formation of fibrin clots may be sufficient to occlude the blood vessels that feed tumor cells, contributing to massive ischemia, vascular infarction, and the subsequent necrosis and apoptosis of neoplastic cells. This approach called as tumor vascular infarction was pioneered by Huang et al. (Science 275:547-550, 1997). Since then, different vascular targeting moieties were linked to a truncated form of human tissue factor (tTF), to generate coaguligands with selective thrombotic activities on tumor neovasculature. In contrast to the wide clinical application of angiogenesis inhibitors and tumor vascular disrupting agents, tTF-NGR is the only example of clinically tested coaguligands. Notably, among these three tumor vascular targeting approaches, tumor vascular infarction is the only modality manifesting long-term curative potential in mice. Translation of this worthy approach has been limited, as induction of thrombosis by TF fusion proteins is leaky. In this review, we describe the clinical significance of tumor vascular infarction, highlight its advantages and disadvantages, and propose a novel strategy for expediting its translation to clinical settings.