Reactive astrocytes and glioblastoma: are there new targets for more effective antitumor therapy?

Abstract

Introduction. Astrocytes in the brain of a healthy person perform a number of protective functions, contribute to maintaining the functional activity of neurons and their synapses. However, in some pathological conditions, they change their phenotype to a reactive one and can both remodel damaged areas and contribute to increased aggression and invasiveness of gliomas.Aim. To comprehensively study the features of reactive astrocytes and the chemo- and radioresistance of gliomas associated with reactive astrocytes.Materials and methods. The authors analyzed articles from the databases Elsevier, pubmed, Scopus, google Scholar, Embase, web of Science, The Cochrane Library, global Health, CyberLeninka and RSCI. when selecting articles, the indexing systems of journals and the citation of articles, the scientific novelty of research, the statistical significance of the results obtained in them were taken into account, publications with duplication of the results of previous studies were excluded. In the course of the study, data on the mutual influence of reactive astrocytes and glioma cells were systematized.Results. Astrocytes of the brain of healthy people are highly variable and heterogeneous, which further complicates the interpretation of published studies. At the same time, reactive astrocytes contribute to an increase in the chemoresistance and radioresistance of gliomas of different degrees of malignancy. At the same time, the exact mechanisms for controlling the interaction between reactive astrocytes and glioma cells, which contributed to less progression and invasion of the tumor or its regression, have not yet been established. However, this direction is now actively developing and is promising due to the possibility of additional effects on gliomas.Conclusion. At the moment, there is no effective treatment that can cope with gliomas, all existing treatment methods are aimed only at increasing the life expectancy of patients with gliomas. The results of recent studies suggest that, probably, the current insufficient effectiveness of chemo- and radiotherapy may be associated with a very close relationship between tumor cells and tumor-associated reactive astrocytes due to their mutual supportive effect. Therefore, the solution to the problem of incurable patients with gliomas may lie in a complex effect on both tumor cells and their microenvironment.

Keywords

• gliomas
• glioblastomas
• reactive astrocytes
• chemoresistance
• radioresistance
• age variability of astrocytes
• temozolomide