Dear Colleagues,

Glioblastoma multiforme (GBM) or grade IV astrocytoma is the deadliest form of brain tumor. To date, the standard therapy consists of a multimodal approach combining surgery, radiation and chemotherapy with temozolomide. However, tumor relapse frequently occurs, and survival rates are poor in patients. GBM’s poor prognosis is also attributable to therapeutic resistance to standard therapy. The therapeutic resistance is mainly due to the presence of glioblastoma stem cells (GSCs) inside the tumor core, and could be dependent on innate differences in clonogenic GSCs’ sensitivity to conventional therapy. GSCs and mature cells reside in specific regions of the cancer mass forming tumor niches, including hypoxic, vascular and perivascular niches that support GSCs’ quiescent status and contribute to create a microenvironmental cue sustaining their pluripotent potential which determines cancer aggressiveness and therapy resistance. The resident cells of the central nervous system and blood-derived elements are recruited into the niches for a functional symbiosis that ensures energy sources, invasiveness, immune escape, and drug resistance to the GBM, allowing its progression.

Furthermore, GBM is characterized by intratumor and inter-patient molecular heterogeneity that may underlie differences in patient sensitivity to therapy and prognosis.

Although the research in this field is rapidly evolving, there is a persistent variability of treatment effectiveness and difficulty in performing early diagnosis. The identification of non-invasive alternatives to standard diagnostic approaches, such as liquid biopsy, as well as novel treatment strategies and effective therapeutic targets, could offer new directions for future therapeutic management.

This Special Issue considers original research articles, review articles, and commentaries on the following themes: i) identification of new molecular targeted and/or prognostic biomarkers for GBM; ii) recent advances in combined therapy to existing gold-standard treatment; iii) ongoing clinical trials in the treatment of GBM.

Prof. Dr. Agata Grazia D'Amico
Prof. Dr. Celeste Caruso Bavisotto
Dr. Assunta Virtuoso
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Brain Sciences is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

• glioblastoma multiforme
• tumor microenvironment
• hypoxic niches
• vascular niches
• liquid biopsy
• extracellular vesicles
• immunotherapy
• glial cells
• neurons
• macrophages