Abstract
The modulation of tumor growth and development in vitro has always been one of the key factors in the research of the malignant transformation, including gliomas, prevalent and most deadly cancers of the brain. Indeed, cellular and molecular biology research employing in vitro model cell-based systems have great potential to advance both the mechanistic understanding and the treatment of human glial tumors, as it facilitates not only the understanding of glioma biology and its regulatory mechanisms Additionally they promise to afford the screening of the putative anti-tumor agents and alternative treatment approaches in a personalized manner, i.e. by virtue of using the patient-derived tumor material for such tests. However, in order to become reliable and representative, glioma model systems need to move towards including most inherent cancer features such as local hypoxia, specific genetic aberrations, native tumor microenvironment, and the three-dimensional extracellular matrix.This review starts with a brief introduction on the general epidemiological and molecular characteristics of gliomas followed by an overview of the cell-based in vitro models currently used in glioma research. As a conclusion, we suggest approaches to move to innovative cell-based in vitro glioma models. We consider that main criteria for selecting these approaches should include the adequate resemblance to the key in vivo characteristics, robustness, cost-effectiveness and ease to use, as well as the amenability to high throughput handling to allow the standardized drug screening.
Highlights
Primary tumors of the central nervous system (CNS) comprise relatively rare oncological pathologies in comparison to other common neoplasms [1]
We suggest that quiescent cancer stem cells (CSCs) can be delineated by co-expression of resistance genes to existing therapy (MGMT, APNG, p16INK4A) [48], normal neuronal precursors genes (HES1, TSC22D1, KDM5B, POU3F2, NFIA and NFIB) [49,50] combined with low activity of the cell cycle genes (IGFBP5, VEGFA, SLC2A3, LGALS3, FAM115C, MT1X, UBC, C4orf3, FAM162A, PPP1R15A, EEF1A1, FTL) [44]
The importance of glioma molecular profiling was underscored by the World Health Organization (WHO) in 2016, when it issued a new glioma classification based on certain mutations in the genes coding for isocitrate dehydrogenases (IDH1, IDH2) and 1p/19q codeletion
Summary
Primary tumors of the central nervous system (CNS) comprise relatively rare oncological pathologies in comparison to other common neoplasms [1]. According to the Central Brain Tumor Registry of the United States (CBTRUS), in the United States the incidence rate of all primary malignant brain and other CNS tumors is 7.15 per 100,000 [3]. An estimated 23,830 new cases of primary malignant brain and other CNS tumors are expected to be diagnosed in the United States in 2018 [3]. Primary malignant brain and other CNS tumors incidence rates were 3.9 cases per 100,000 males and 3.0 cases per 100,000 females. For low-grade gliomas, the overall survival rate is substantially higher, being 16 years for oligodendroglioma patients and 8 years for astrocytoma patients [11]; relapses occur in approximately half of the cases [12]. The 5-year survival estimated by RARECARE project is around 5 and 43% for high and low grade astrocytomas respectively, while for oligodendrogliomas this index is reaching 30 and 65% for high and low tumor grades, respectively [14]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
