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Cancer growth is driven by the complex interplay between tumor cells and their supportive microenvironment. However, this interaction is still not fully understood, especially for gliomas, which are very aggressive tumors growing in the complex brain milieu. Here, I will present some recent results from our group showing how the genomic background of gliomas controls tumor progression by modifying the plasticity of neoplastic cells and their capacity to shape their vascular landscape. These data allows us to suggest a novel stratification of gliomas: from the less aggressive IDHmut tumors, with a “normalized” vasculature, to the highly angiogenic EGFRmut gliomas, where tumor cells can act as pericytes, reinforcing the vessel walls and fueling the proliferation of neoplastic cells. In the absence of these tumor-derived pericytes, the blood-brain-barrier is disrupted and hypoxic signals are induced, as an alternative way to promote tumor progression.
These results place the vascular properties at the top of the glioma hierarchy, controlling the aggressiveness of the tumors, as well as the entrance and the function of immune cells. Moreover, our most recent studies suggest these vascular alterations are associated with the neuronal loss observed in brains harboring gliomas, which share some similarities with the neurodegenerative processes that occur in other neuropathologies. We believe that our data have important implications for the clinical management of glioma patients, from tumor classification to treatment. Furthermore, they highlight the relevance of understanding the complex brain microenvironment to decipher the etiology of seemingly different neurological diseases.
Dr. Sánchez-Gómez graduated in Chemical Sciences at Universidad Autónoma de Madrid, where she also got her PhD in Biochemistry in 2000, working in the lab of Dr. Jorge Moscat. During her postdoctoral training at New York (Lab of Dr. Ariel Ruiz i Altaba), Geneva and Valencia (Lab. of Dr. Isabel Fariñas) Universities, she participated in relevant studies defining the molecular mechanisms that control the behavior of normal and tumorigenic neural stem cells. Those include for example the Shh pathway or the PEDF and DYRK1A molecules. In 2008 she started the Neurooncology Unit at ISCIII (Instituto de Salud Carlos III) with a focus on brain tumors, particularly gliomas. Working in close collaboration with clinicians, they have studied novel therapeutic strategies, especially those inhibiting EGFR, one of the key pathways deregulated in such tumors. During the last years, she got interested in deciphering the crosstalk between tumor cells and their microenvironment (vascular and inflammatory cells), which determines the aggressiveness of gliomas. The results from her lab suggest that the genetic status of IDH and EGFR dictates the plasticity of tumor cells, and the vascular phenotype of gliomas. Although these tumors are seemingly different from other brain pathologies, their results suggest as well that alterations of the permeability of the blood vessels could contribute to the progression of many of these diseases.
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