Tumour vascular targeting

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.

High expression of prostate-specific membrane antigen in the tumor-associated neo-vasculature is associated with worse prognosis in squamous cell carcinoma of the oral cavity

“…2,3 PSMA has been suggested as a potential candidate for direct tumorspecific vascular targeting. 2 Interestingly, neo-vascular PSMA expression levels appear to differ significantly between different tumor types. [9][10][11][12]24,25 Here, we show that in oral squamous cell carcinoma high neo-vascular PSMA expression can only be detected in a subset of lesions.…”

“…1,2 Several therapeutic approaches have therefore focused on inhibiting neo-angiogenesis and have shown sustainable clinical responses. 2 Such anti-angiogenic therapies can either interfere with signal transduction pathways or signaling molecules that regulate vessel formation and vessel growth or directly target tumor-associated endothelial cells. 3 It is of particular interest that several markers have been characterized that show a specific expression in tumor-associated endothelial cells, but not in normal endothelial cells.…”

“…3 It is of particular interest that several markers have been characterized that show a specific expression in tumor-associated endothelial cells, but not in normal endothelial cells. 2,4,5 One such molecule, that shows high expression in the tumor-associated neovasculature is prostate-specific membrane antigen (PSMA, also known as folate hydrolase 1, FOLH1). PSMA is a metallo-protease that was originally cloned from human prostate carcinoma cells and has been shown to be overexpressed in the vast majority of prostate cancers.…”

Endocannabinoids as emerging suppressors of angiogenesis and tumor invasion (Review)

“…VEGF/VEGF receptor pathway represents a key player in tumor-induced angiogenesis and, consequently, tumor progression and metastasis. The humanized anti-VEGF monoclonal antibody bevacizumab has been recently approved for cancer treatment and results are encouraging even if not untroubled (23,24). Endocannabinoids warrant further investigation since they have been clearly shown to interfere with the VEGF pathway in different systems and may provide a useful tool to target VEGF in cancer.…”

Interfering with pH regulation in tumours as a therapeutic strategy

“…In normal tissues and at pH i values of around 7.0, cells typically produce the 'small' tenascin C splice isoform, which does not include domains A1 to D. When cells are artificially exposed to basic pH values -for example, in cell culture experiments, fetal tissues (which typically have basic pH values of around 7.4-7.5 units) or in aggressive forms of cancer -changes of 0.2-0.3 pH units in the pH i value lead to a complete switch towards the formation of the 'large' tenascin C splice isoform, which includes domains A1 to D 11,12 . Interestingly, tenascin C splice isoforms are commonly found in the tumour stroma and/or around tumour blood vessels [92][93][94][95][96][97][98] and serve as markers of angiogenesis 99 . The regulation of alternative splicing of tenascin C is complicated by the observation that the extra domain C displays a more restricted pattern of expression than the other domains between A1 and D 100,101 .…”