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  • Review Article
  • Published:

Tumour vascular targeting

Key Points

  • Proteins that are expressed on the tumour vasculature but not on the vasculature of normal tissues can be used for imaging and targeting purposes.

  • Vascular targets include proteins expressed on the endothelial cell, such as DELTA4 or ROBO4, as well as those that are secreted into the stroma around the vessels, such as the differentially spliced isoforms of fibronectin and tenascin.

  • Ligands for the vascular targets include antibodies and possibly certain aptamers, such as modified DNA.

  • Delivery of a suitable bioactive molecule (toxin, cytokine, etc.) coupled to a targeting ligand can be used to eradicate solid tumours.

  • In the longer term, it is possible that vascular targets could be used to develop a cancer vaccine.

Abstract

It is now accepted that the growth of solid tumours is dependent on their capacity to acquire a blood supply, and much effort has been directed towards the development of agents (known as anti-angiogenics) that disrupt this process. More recently, it has become apparent that targeted destruction of the established tumour vasculature is another avenue for exciting therapeutic opportunities. In this article, we present evidence that vascular targeting is an effective antitumour strategy in animal models, describe strategies for identifying putative tumour vascular targets and discuss future prospects for vascular targeting in the clinic.

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Figure 1: Illustration of the concept of tumour vascular targeting.
Figure 2: Some well-characterized tumour endothelial markers.
Figure 3: Microscopic analysis of tissue and tumour sections.
Figure 4: Immunoscintigraphic detection of a solid tumour with a radiolabelled antibody fragment against extra-domain B (EDB).

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Acknowledgements

The authors would like to acknowledge funding from Cancer Research UK (R.B.) and the European Union (P.N. and R.B). D.N. is grateful to the following institutions for the funding of his research in oncology: ETH Zurich, the Swiss National Science Foundation, the Bundesamt für Bildung und Wissenschaft for EU Projects, the Schweizerische Krebsliga and the Gebert-Rüf Foundation.

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DATABASES

Entrez Gene

ADM

ASPP1

CD44

CD66

CD105

DEL1

EDN1

EndoPDI

ERBB2

FLT1

GA733-1

GP34

HES

KDR

LRRC19

PSMA

ROBO4

STC1

TEM1

TEM5

TEM7

TEM8

TGFβ

TIE2

TNF

VEGF

Glossary

MHC CLASS II

The major histocompatibility complex (MHC) is a large gene cluster that encodes various components of the immune system, including the histocompatibility antigens (comprised of classes I, II and III) and components of the complement system. Class II molecules have two MHC-encoded polypeptides and their expression can be induced on endothelium in response to inflammatory cytokines.

DISCOIDIN DOMAIN

A three-dimensional protein motif originally found in a carbohydrate-binding protein that was isolated from the slime mould Dictyostelium discoideum. Discoidin domains are thought to interact with components of the extracellular matrix.

APTAMERS

Derived from the Latin aptus, meaning, 'to fit', aptamers are specific RNA or DNA oligonucleotides or proteins that can adopt many three-dimensional shapes. Aptamers can, therefore, be produced to bind tightly to a specific molecular target.

SYNGENEIC

Genetically identical. A term usually applied to grafts made of cells transferred within an inbred strain.

AUGER EMITTER

An atom that can eject an electron without the emission of an X- or gamma-ray photon. The energy of an Auger electron usually permits only short-range tissue penetrance.

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Neri, D., Bicknell, R. Tumour vascular targeting. Nat Rev Cancer 5, 436–446 (2005). https://doi.org/10.1038/nrc1627

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