Cellular Plasticity and Tumor Microenvironment in Gliomas: The Struggle to Hit a Moving Target

Brain tumors encompass a diverse group of neoplasias arising from different cell lineages. Tumors of glial origin have been the subject of intense research because of their rapid and fatal progression. From a clinical point of view, complete surgical resection of gliomas is highly difficult. Moreover, the remaining tumor cells are resistant to traditional therapies such as radio- or chemotherapy and tumors always recur. Here we have revised the new genetic and epigenetic classification of gliomas and the description of the different transcriptional subtypes. In order to understand the progression of the different gliomas we have focused on the interaction of the plastic tumor cells with their vasculature-rich microenvironment and with their distinct immune system. We believe that a comprehensive characterization of the glioma microenvironment will shed some light into why these tumors behave differently from other cancers. Furthermore, a novel classification of gliomas that could integrate the genetic background and the cellular ecosystems could have profound implications in the efficiency of current therapies as well as in the development of new treatments. This research was funded by Asociación Española contra el Cancer, Junior investigator grant number INVES192GARG to R.G. and by Ministerio de Economía y Competitividad grant number RTI2018-093596-B100/FEDER to P.S.-G. Sí