Exploring and exploiting the vasculature in brain tumors

Glioblastoma (GBM) and brain metastases (BrM) represent the most aggressive and lethal central nervous system neoplasms, with median survival typically below one year. Recent studies have revealed the importance of the brain tumor microenvironment (TME), notably diverse immune cells, in regulating cancer progression in both primary and metastatic brain malignancies. The blood-brain barrier (BBB) is another critical TME component formed by endothelial cells, mural cells, astrocytic end-feet, and closely-associated microglial cells. Metastasizing cancer cells can use different strategies to traverse the BBB, and once they have successfully seeded and colonized the brain, they can exploit the vasculature for their own benefit, forming the so-called blood-tumor barrier. We investigate these two aspects of vascular alterations in brain tumors, focusing first on the mechanisms used by tumor cells to metastasize to the brain, and second, exploring the processes underlying tumor vascularization in primary and metastatic brain tumors. Our studies, which include clinical sample analysis and preclinical studies in mouse brain tumor models, provide important insights into the complex interactions between the vasculature, immune cells, and cancer cells, with high relevance for designing therapeutic interventions.