Novel Concepts of Glioblastoma Therapy Concerning Its Heterogeneity

Abstract

Although treatment outcomes of glioblastoma, the most malignant central nervous system (CNS) tumor, has improved in the past decades, it is still incurable, and survival has only slightly improved. Advances in molecular biology and genetics have completely transformed our understanding of glioblastoma. Multiple classifications and different diagnostic methods were made according to novel molecular markers. Discovering tumor heterogeneity only partially explains the ineffectiveness of current anti-proliferative therapies. Dynamic heterogeneity secures resistance to combined oncotherapy. As tumor growth proceeds, new therapy-resistant sub clones emerge. Liquid biopsy is a new and promising diagnostic tool that can step up with the dynamic genetic change. Getting a ’real-time’ picture of a specific tumor, anti-invasion and multi-target treatment can be designed. During invasion to the peri-tumoral brain tissue, glioma cells interact with the extracellular matrix components. The expressional levels of these matrix molecules give a characteristic pattern, the invasion spectrum, which possess vast diagnostical, predictive and prognostic information. It is a huge leap forward combating tumor heterogeneity and searching for novel therapies. Using the invasion spectrum of a tumor sample is a novel tool to distinguish between histological subtypes, specifying the tumor grades or different prognostic groups. Moreover, new therapeutic methods and their combinations are under trial. These are crucial steps towards personalized oncotherapy.

Role of Transmembrane Water Exchange in Glioma Invasion/Migration: In Vivo Preclinical Study by Relaxometry at Very Low Magnetic Field

“…Making these cells visible is therefore a major clinical need for neurosurgeons to optimize glioma resection. Many efforts are currently devoted to accurately delineating the peritumoral regions, also exploiting peculiar characteristics of the microenvironment [ 4 , 5 ]. Additionally, peritumoral regions are known to promote cell invasion, a mechanism considered to be one of the leading causes of death from cancer.…”

Serum microRNA-4297 is a sex-specific predictive biomarker of glioma grade and prognosis

“…Furthermore, early identification of glioma recurrence is another challenge for the postoperative care of glioma patients. It has been well-recognized that the histologic changes alone could not provide accurate and timely information about the development and progress of the glioma ( 1 , 27 ). We found serum miR-4297 levels showed no remarkable disparities among diffuse astrocytoma (DA), anaplastic astrocytoma (AA), and anaplastic oligodendroglioma (AOD), oligodendroglioma (OD), and glioblastoma (GBM).…”

Immunosuppressive cells in oncolytic virotherapy for glioma: challenges and solutions

“…Glioma, the most common primary central nervous system (CNS) tumor in adults, is characterized by aggressive clinical-biological behavior, with low-grade gliomas eventually progressing to CNS WHO grade 3/4 gliomas and resulting death ( Claus et al., 2015 ). Glioblastoma ( Louis et al., 2021 ), the most lethal type of glioma, is resistant to conventional therapies and shows invasive, intratumoral heterogeneity and stem-like phenotypic plasticity ( Liu et al., 2018 ; Perus and Walsh, 2019 ; Prager et al., 2020 ; Hutoczki et al., 2021 ; Nicholson and Fine, 2021 ; Knudsen et al., 2022 ). The median survival time is less than two years despite multimodality treatment options, such as maximum safe surgical resection, chemotherapy, radiotherapy, and other new treatment strategies ( Tan et al., 2020 ).…”