The understanding of tumor angiogenesis, basic component for the growth of solid tumors and for the development of metastasis, has suffered enormous advances during the last decades. In fact this research contributed very significantly to address the current challenges to properly attack tumor heterogeneity. Our efforts have been focused to unveil the contribution of extracellular proteases according to their modulatory capacity of the extracellular framework, quite far from the simplistic view of a scaffold and maintenance service. Together with the functional characterization of every existing extracellular protease, it is required to envision such proteolytic activity in a specific scenario, highlighting the relevance of hypoxic-sensitive pathways. The detailed characterization of the tumor microenvironment and its remodelling by proteolysis, together with the extracellular and cellular components of the vascular niche, are a current priority, with special relevance for the understanding of mechanisms of drug resistance that certain tumors develop.
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