Researchers at the 12 de Octubre Hospital of Madrid have identified the cause that causes a type of malignant brain tumor, known as Glioblastoma, is more aggressive and causes lower survival in men than in women. The reason that generates this difference is the necrosis or death of tumor cells which gives rise to an inflammatory reaction characterized by infiltration of a type of immune system cellcalled myeloid suppressor cell (MDSC), which, instead of attacking malignant cells, helps their growth, reports the Madrid hospital.
These cells would be much more present in men because, in their case, the necrosis and inflammation produced by the tumor is much greater. According to Dr. Berta Segura, a postdoctoral fellow in the Neuro-Oncology Research Group of the Hospital 12 de Octubre i+12 Research Institute, the differences in incidence and aggressiveness of different types of cancer between men and women are widely recognized, but in most cases the cause has not been understood enough to establish a specific treatment for each sex.
73 tumors
“Glioblastoma is the most common malignant brain tumor and is a good example of this. In this context, the objective of this study was to investigate the tumor processes that explain these differences depending on gender.” The researchers explain that it is a retrospective study of patients with Glioblastoma that was stratified according to sex and in which a cohort of 73 tumors.
The researchers observed that, when the tumor generates necrosis, substances are released that activate the recruitment of the immune system
They observed that, when the tumor generates necrosis, substances are released that activate the recruitment of the immune system. In the case of men, greater necrosis occurs, which generates a more toxic microenvironment and a more massive and aggressive response in terms of inflammation by immune cells called MDSC.
MSDC cells – immunosuppressive cells – describe, are produced in the bone marrow and are characterized by the ability to suppress the function of different components of the immune systemso that, instead of attacking the tumor, they help its growth.
More aggressive in men
The origin of glioblastomas more aggressive in the group of men is due to the tumor’s lack of ability to generate functional tumor blood vessels, which supply the arrival of oxygen and nutrients necessary for the cells, leading to thus tumor necrosis, the researchers indicate.
Even so, “the most surprising thing is that there is a group of men who do not present these tumor characteristics and in them this brain tumor has a much lower aggressiveness, becoming very similar to what women have,” explains Segura.
The treatment
The researchers analyzed, on the other hand, the therapeutic effect of ‘Bevacizumab’ treatment in a retrospective cohort of 36 tumors according to sex differences. This drug inhibits a molecule, called VEGFA, they point out, which is involved in the process of generating tumor blood vessels. This treatment has had positive results in other types of cancer, but not in Glioblastoma. Although it did not prolong survival, it did improved the patient’s quality of life, reducing neurological deficit and headache. For this reason, today it is used in the second line.
However, when they divided the patients according to the groups described in their study, on the one hand, the women and, on the other, the two groups of men, the result was that precisely the men with the greatest necrosis and the worst survival were the ones with the greatest benefit they obtained from the treatment. The explanation is that the medicine has a positive effect only in the situation where the tumor does not generate good vessels and triggers toxic inflammation.
Molecular biomarkers
According to him Dr. Ricardo Garginifrom the same i+12 research group and another of the authors of the scientific article, “this means that we can establish a set of molecular biomarkers, based on the level of necrosis and tumor inflammation, that could be used to predict the response to this treatment.
The next step is to open a clinical trial so that ‘Bevacizumab’ is administered, along with chemotherapy and radiotherapy, as a first-line treatment
For her part, Dr. Segura concludes that the next step is to open a clinical trial so that ‘Bevacizumab’ can be administered, along with chemotherapy and radiotherapy, as first-line treatment in these types of patients. “On the other hand, we want to demonstrate the need to stratify the trials taking into account gender bias and, within that category, other characteristics that make the treatments have different effects,” he ditches.