- Prof. Francesco Pezzella
- Nuffield Division of Clinical Laboratory Science, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.
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Special Issue Introduction
Hailed as the big breakthrough in cancer treatment during the nineties and the first decade of the present century, the introduction of antiangiogenic therapy has failed to deliver the exceptional results announced. On the basis that this failure has been the assumption, the understanding of the biology of the relationship between cancer and blood vessels was complete. It is somehow a pity that big promises were made, as the work from those years is seen now, more than anything else, as a disappointment. Still, it is wrong to look at it as an impasse, as it has been laying the foundation for a more detailed study of such a complex aspect of cancer and starting to deliver a great deal of knowledge about vascular biology. Although the all idea that angiogenesis is a Hallmark of Cancer turned out to be simply wrong, Folkman’s ideas and work, already in the mid-1990s, were stimulating other groups to work in this area. Following Folkman’s work, new aspects have emerged, like the non-angiogenic cancer growth, which exploits pre-existing vessels by means of vascular-co-option, or cancer cells forming a vascular channel, like in the vascular mimicry. Early cancer stem cells have been found to form normal-looking vessels, although deriving from the neoplastic clone. The discovery of genetic instability of the actual normal endothelial cells has led to demonstrate that the intratumor endothelial cells are not necessarily genetically stable. Therefore, the idea that antiangiogenic treatment could always work on these “stable” endothelial cells resulted in being wrong. Furthermore, angiogenic pathways are heterogeneous, e.g., targeting VEGF pathway does not eliminate the possibility to preserve angiogenesis through other mechanisms. Finally, we now know that intratumor endothelium is also involved in immune regulation and needs to be taken into account in planning immune therapy. This new wealth of data is currently defining a more complex picture of the relationship between cancer and blood vessels. But on one side, all this is useful to explain why the universal use of antiangiogenic drugs is not the answer; it is also unveiling a variety of new targets for treatment. Therefore, the present Special Issue invites all the researchers investigating the relationship tween tumors and their vascularization to contribute their papers, looking at all the possible aspects of this complex piece of biology to open the way to new therapeutic approaches.
Submission Deadline30 Jun 2022