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Tumor vascular infarction: prospects and challenges

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Abstract

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.

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Abbreviations

AIs:

Angiogenesis inhibitors

VTAs:

Vascular targeting agents

VDAs:

Vascular disrupting agents

IFP:

Interstitial fluid pressure

STVTs:

Selective tumor vascular thrombogens

PR:

Partial tumor remission

CR:

Complete tumor remission

VCAM-1:

Vascular cell adhesion molecule

PS:

Phosphatidylserine

PSMA:

Prostate-specific membrane antigen

S.C:

Subcutaneous

i.v:

Intravascular

GFP:

Green fluorescent protein

HAPs:

Hypoxia-activated prodrugs

NG2:

Nerve/glial antigen 2

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Acknowledgment

The authors would like to thank Iranian National Science Foundation ((INSF), grant number 90007316) for financial support of this work.

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Authors and Affiliations

  1. Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran

    Rana Jahanban-Esfahlan, Khaled Seidi & Nosratollah Zarghami

  2. Department of Clinical Biochemistry, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

    Nosratollah Zarghami

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  1. Rana Jahanban-Esfahlan
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  2. Khaled Seidi
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Correspondence to Nosratollah Zarghami.

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Jahanban-Esfahlan, R., Seidi, K. & Zarghami, N. Tumor vascular infarction: prospects and challenges. Int J Hematol 105, 244–256 (2017). https://doi.org/10.1007/s12185-016-2171-3

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  • DOI: https://doi.org/10.1007/s12185-016-2171-3

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