2023-08-03 18:10:29
A genetic ‘barcode’ that allows you to trace every cell of glioblastoma, the most widespread and aggressive brain cancer that affects around 1,500 Italians every year, following its evolution from the earliest stages and paving the way for new treatment options. This is the strategy described in ‘Cancer Cell’ by a team of researchers from the Irccs hospital Policlinico San Martino in Genoa and the Department of Experimental Medicine of the University of the Ligurian capital, led by Paolo Malatesta, with the main contribution of Davide Ceresa. The study was conducted in an experimental mouse model.
Thanks to advanced molecular biology techniques, such as the analysis of the transcriptome, i.e. the set of genes transcribed in a cell, and to computational models that have made it possible to simulate the evolution of glioblastoma on the computer – explains a note – it has been possible to study the factors that influence their growth, such as the dynamics of diversification and selection that take place between the different clones of neoplastic cells. A new hope to understand and fight a form of cancer still little known in its early stages. More frequent in men than in women (ratio of 1.6 to 1) and in the age group between 45 and 75 years, glioblastoma represents 45% of brain tumors. Ionizing radiations, such as X-rays and gamma rays, are recognized as a risk factor for the appearance of this tumour, which gives symptoms only when the diseased mass, expanding, increases the pressure and dilates the blood vessels causing disturbances such as headaches increasing intensity, vomiting and seizures.
“The therapy is extremely complex and, unfortunately, does not yet offer a definitive solution – says Malatesta, co-author of the study, head of the San Martino Experimental Neuro-oncology Program and professor of Molecular Biology at the Genoese university – Currently the life expectancy for patients with glioblastoma remains less than 3 years. Improved treatment could, however, come from a better understanding of tumor development, which is very heterogeneous from a cellular point of view and is poorly understood in its early stages”.
To better understand the evolution of the disease from the earliest stages, the scientists of the San Martino Polyclinic have developed a model of glioblastoma in which it was possible to trace every single neoplastic cell, in time and space. “We have introduced a sort of bar code into the cells to be monitored – explains Ceresa, co-author of the study and researcher at the Genoese Irccs – a particular string of DNA which, in addition to inducing the disease, also allows for subsequent tracing of the tumor cells , following them thanks to sophisticated sequencing techniques”.
“By monitoring the evolution of the neoplastic cells – reports Ceresa – we have observed, for example, that within the first month of the mutation in a tumor sense, most of the clones of neoplastic cells disappear; by comparing the data on real tumor growth with those obtained thanks to computational models able to simulate it in different scenarios and conditions, we verified the existence of a very strong clonal selection in the early stages of development of glioblastoma, which is maintained also in later stages.The dynamics of cell competition therefore seem to play a primary role in determining the development of glioblastoma, even in more advanced stages of its growth. Basically, through sophisticated programs that allow us to simulate the growth of the tumor, we were able to test our hypotheses by comparing the simulations with the real development of the neoplasm”.
Thanks to the analysis of the transcriptome, at the level of each single cell, the scientists have also identified the Myc gene, already known for its role in other tumors, as one of the major culprits of this process of clonal selection. “The decrease in Myc expression – highlights Malatesta – is sufficient to initiate competition dynamics between clones of malignant cells even in gliomas implanted in the brain of experimental animals, confirming their importance in the evolution of the disease. This new approach, which combines innovative molecular biology techniques with the use of advanced computational models, has allowed us to gather important information on glioblastoma, but above all paves the way for a better understanding of the mechanisms of development of this tumour. stages was hitherto impossible, using conventional techniques that allow it to be studied only retrospectively, but clonal tracing and transcriptomic analysis techniques will now be able to provide new and important information that will serve to better understand and combat it”.
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