Gastrointestinal tumors are responsible for more cancer-related fatalities than any other
type of tumors, and colorectal and gastric malignancies account for a large part of these diseases.
Thus, there is an urgent need to develop new therapeutic approaches to improve the patients’ outcome
and the tumor microenvironment is a promising arena for the development of such treatments.
In fact, the nature of the microenvironment in the different gastrointestinal tracts may significantly
influence not only tumor development but also the therapy response. In particular, an important
microenvironmental component and a potential therapeutic target is the vasculature. In this context,
the extracellular matrix is a key component exerting an active effect in all the hallmarks of cancer,
including angiogenesis. Here, we summarized the current knowledge on the role of extracellular
matrix in affecting endothelial cell function and intratumoral vascularization in the context of colorectal
and gastric cancer. The extracellular matrix acts both directly on endothelial cells and indirectly
through its remodeling and the consequent release of growth factors. We envision that a deeper
understanding of the role of extracellular matrix and of its remodeling during cancer progression is
of chief importance for the development of new, more efficacious, targeted therapies
