In search of normality: looking for molecular strategies to repair cancer blood vessels

Abstract

Defects in the adhesion of endothelial cells (ECs) to each other and to the extracellular matrix (ECM) are primarily responsible for the structural and functional abnormalities characterizing blood vessels of most solid tumors. In addition to promote tumor cell intravasation and metastatic dissemination, abnormal tumor blood vessels hinder the effective delivery of therapies and decrease the efficacy of radiotherapy and immunotherapy. The development of treatments aimed at normalizing the tumor blood vasculature is therefore needed. To this aim, it is crucial to identify the signal transduction pathways that govern the adhesion dynamics of ECs and are altered in the abnormal vasculature of tumors, to therapeutically target them. I will illustrate our contributions to the identification of the biochemical mechanisms that control physiological EC adhesion dynamics and are disrupted in abnormal cancer blood vessels. In this context, we unveiled how different secreted protein ligands and their receptors, originally identified for their ability to control axonal guidance, also drive normal vascular morphogenesis, and are lost during cancer progression. The creation of the corresponding rationally modified ligands may represent an opportunity to create recombinant proteins that could be therapeutically exploited to fix tumor vascular abnormalities.

* PER PARTECIPARE online:

https://us02web.zoom.us/j/88477695499?pwd=14LGHlSoanEHHql1W7vGjyl2gbvgzV.1

Meeting ID: 884 7769 5499

Passcode: 471391