Glioblastoma: Recent Advances and Challenges

Dear Colleagues,

Glioblastoma (GBM) is the most common and most malignant of all primary tumors of the brain and nervous system. To date, treatments with standard radiation and chemotherapy have provided little additional survival benefits to patients with GBM. Unlike other cancers, there are limited FDA-approved treatments for GBM, and different treatment modalities with proven success in preclinical settings have not been successfully translated to the clinic.Overall, more treatments options are critically needed specifically to target GBM. Various treatment options for GBM that have been tested still have significant limitations regarding brain tumor penetration and the heterogeneity of this cancer. New cancer therapeutics such as immunotherapies are still being evaluated for the treatment of GBM. Better understanding in GBM cancer biology and tumor microenvironment would considerably improve new treatments for GBM.

In this Special Issue, advances in the treatment of GBM will highlight needed areas of studies to enhance treatment options for patients with GBM from a basic and clinical standpoint. 

Dr. P. Leia Nghiemphu
Guest Editor

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• glioblastoma
• cancer immunotherapy
• brain tumor microenvironment
• molecular targeted therapy
• GBM

Title: Glioblastoma Multiforme Therapy: Present and Future
Authors: María A. Marqués-Torrejón1*, Paz Moreno-Murciano2, María Oriol-Caballo2,3, Rafael López-Blanch2,3, Alba Loras1, Luis G. Gonzalez-Bonet4, Conrado Martinez-Cadenas5, José M. Estrela2,3,6, and Elena Obra
Affiliation: 3Department of Medicine, Faculty of Medicine and Odontology, University of Valencia, 46010 Valencia, Spain 2 Scientia BioTech S.L., 46002 Valencia, Spain 1 Cell Pathophysiology Unit (UFC), Department of Physiology, Faculty of Medicine and Odontology, University of Valencia, 46010 Valencia, Spain 4 Department of Neurosurgery, Castellon General University Hospital, 12004 Castellon, Spain 5 Department of Medicine, Jaume I University of Castellon, 12071 Castellon, Spain 6 Department of Physiology, Faculty of Pharmacy, University of Valencia, 46100 Burjassot, Spain *Correspondence: torrejom@uji.es M.A.M.-T.), Tel.: +34-641774524; elena.obrador@uv.es (E.O.), Tel.: +34-963864646
Abstract: The glioblastoma multiforme (GBM, also called grade IV astrocytoma) is the most aggressive and prevalent brain tumor that forms from astrocytes of the brain and spinal cord. It is more frequent in adults and affects the brain more than the spinal cord. The standard of care for newly diagnosed glioblastoma multiforme (GBM) involves surgical resection (if feasible), concurrent radiotherapy and chemotherapy (temozolomide seems to work better by sensitizing the GBM cells to radiation), targeted therapy in recurrent GBM (e.g. bevacizumab, which selectively binds to the VEGF and reduces the growth of blood vessels that supply the tumor with nutrients and oxygen), with or without tumor treating fields (mild electrical fields that pulse through the skin of the scalp aiming to interrupt cancer cells' ability to divide). Despite multimodality treatment, recurrence is almost universal with a median survival of <2 years. Ongoing research, aiming to change this grim prognosis, includes targeted therapies interfering at different signaling mechanisms (PARP, CDK4/RB1/P16ink4, TP53/MDM2/P14arf, PI3k/Akt-PTEN, RTK/RAS/RAF/MEK), immunotherapies (checkpoint inhibitors, vaccines, CAR T cells, NK cell-based therapy), oncolytic virotherapy (specific genes are delivered into target cells with viral vectors to induce oncolysis and the host immune response), nanotherapies (nanometric structures having active anti-GBM agents such as immune cells, chemotherapeutic/anti-angiogenic drugs or sensitizers, or molecules which target GBM cellular receptors/angiogenic blood vessels or open the BBB), and treatments based on the use of non-ionizing energies (laser interstitial thermal therapy, high intensity focused ultrasounds and electroporation). The aim of this review is to discuss the advances and limitations of the current therapies, and to present novel approaches which are under development or following clinical trials. Keywords: glioblastoma multiforme, targeted therapies, immunotherapies, viral therapies, nanotherapies, non-ionizing radiations