The extracellular matrix (ECM) is the central element of a pericellular network of bioactive molecules. It orchestrates molecular interactions, availability and activity, acting as a key regulator of cell functions and complex biological processes, including physiological and pathological angiogenesis. The ECM serves as a source of both stimulatory and inhibitory angiogenesis regulatory factors. The observation that several endogenous inhibitors of angiogenesis derive from the ECM proves its importance in physiological angiogenesis, and point to the ECM as a precious source of therapeutic agents for angiogenesis-driven diseases, including cancer growth and metastatic dissemination. This review focuses on the different approaches to exploit ECM molecules for designing tools for therapeutic inhibition or monitoring of pathological angiogenesis, with particular focus on antineoplastic therapy, and emphasis on peptides of ECM moieties and mimetic small molecules.
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