A group of Italian scientistsi made an important discovery regarding the medulloblastoma: the mechanism that gives rise to one of the most aggressive forms of this pathology has in fact been discovered. Thanks to a research team fromInfant Jesus pediatric hospital from Rome, in collaboration with University of Tor Vergata And Sapienza of Rome and of Trento, It has been possible to develop 2 drugs that have the potential to block cancer and metastasis.
There Research was published in the international scientific journal ‘Acta Neuropathology.
Medulloblastoma: Here’s what the research says
In Italy, medulloblastoma is diagnosed in 7 out of a million children. The survival rate is 80% in the most invasive forms, while in subjects with a more severe diagnosis it unfortunately drops to 30/60%. The neoplasm tends to develop in the cerebellum, the area of the nervous system that has the function of monitoring and coordinating movements.
As for the past research, the therapeutic approaches against medulloblastoma involved the surgical removal of the tumor tissue, and subsequently contrasted with radiotherapy and chemotherapy. However, what prevents it from being treated is the presence of cancer stem cells that neither radiotherapy nor chemo are able to counteract and not only that, these cells have the ability to insinuate and spread in the spinal cord of children.
Fortunately, a new frontier is opening up for the treatment of this terrible pediatric cancer, in particular for that of ‘Group 3’, which has the highest percentage of fatal outcome, which unfortunately occurs in more than 40% of cases within 5 years of diagnosis.
The group of experts identified a new molecular dynamics, the alteration of which generates the aggressiveness of medulloblastoma. However, the scientists of the Infant Jesus revealed that in the Group 3 tumor the protein Amber1 it is produced at excessive levels and, consequently, all the processes it regulates (autophagy and stem identity) function abnormally.
Because of overproduction of Amber 1, the modality exploited by the cells to get rid of the damaged components (autophagy) increases and the cancer cells take advantage of the situation created to survive and proliferate. Not only, the overabundance of this protein keeps the cells in a stem condition which on the one hand helps them to replicate in an uncontrolled manner, pouring into the tissues of origin to form large tumor masses, and on the other hand it helps them in their ability to infiltrate and create new colonies or metastases.
Thanks to this analysis, the team of scientists showed that the combination of two drugs (an inhibitor autophagy and a factor inhibitor of stemness Stat3) allows to stop only the growth of the tumor mass, but also the mechanism that causes the metastases. Amber 1 had already been identified by the same group of experts as the Infant Jesus as a powerful tumor suppressor in other pediatric tumors but also in adults, given its direct function of regulating the cell cycle.
This important discovery makes it a target of considerable importance: “Many children already present with metastases at the time of diagnosis, making it essential to develop more effective therapies – has explained Cecconi – For patients with group 3 medulloblastoma, who have an often poor prognosis, there is an urgent need to integrate new treatment options and, if confirmed in clinical application, our results could lead to personalized therapy against this aggressive form of brain tumor “.