He glioblastoma it is the most common type of brain tumor; It is estimated that it affects between 2 and 5 people in 100,000. Its incidence reaches a peak in the age group between 55 and 85 years, but it is increasingly occurring in all age groups. What is most worrying is that this increase cannot be attributed solely to the improvement in diagnostic techniques, which suggests that there is some environmental factor behind it.
Senescent cells in the brain
In order to unravel the mysteries behind this dangerous cancer, a team of researchers led by doctoral student Alexa Saliou, from the Sorbonne University (France), has examined the tumors of 28 patients from tissue samples removed during surgeries. Among other elements, they were looking for senescent cells or aged; This has been a widely studied approach in recent times, since despite the fact that in certain cases senescence seems to contribute to the antitumor response of the human body, there is evidence that this process could contribute to the development of certain tumors.
As these authors detail in an article published in the academic world Nature communicationssenescence is the loss of the ability of cells to divide. This, as we noted, prevents malignant cells from reproducing, and for this reason it has been hypothesized that it could have an antitumor effect.
However, when cells enter this phase, they secrete various types of molecules, some of which may have effects such as stimulating the immune system or, conversely, inducing the formation of blood vessels that contribute to tumor irrigation. In the long term, these molecules can promote the destruction of the extracellular matrix (which allows the organization of cells into tissue) and the proliferation of malignant cells.
A new way to treat cancers
In this way, they effectively found senescent cells in tumors, in variable proportions and of different classes (tumoral, glial, and immune). These were located mainly around the areas of malignant cell proliferationas well as in cells with necrosis.
A later experiment in animal models (mice) with glioblastoma, in which part of the senescent cells of the tumor were suppressed, showed that in this way it is possible modulate the action of the immune system in the tumor and extend the life expectancy of the animal. They then defined a characteristic signature of senescence based on the expression of 31 genes, and verified that it was identical in humans.
This not only influences the relevance of senescence risk factors (genotoxic or DNA-damaging events; for example, smoking or chemotherapy) in the development of glioblastoma, but also sheds light on a potential new therapeutic avenue through of some drugs in development known as senolytics. Thus, the authors state, if senolytics capable of crossing the blood-brain barrier are found, they could be combined with traditional treatments to improve the efficacy of the latter.
References
Salam, R., Saliou, A., Bielle, F. et al. Cellular senescence in malignant cells promotes tumor progression in mouse and patient Glioblastoma. Nature Communications (2023). DOI: https://doi.org/10.1038/s41467-023-36124-9