It is the most common malignant brain tumor in children. And a team of Italian scientists paves the way for new hope for its cure. Objective: to remove the legs on which he runs, to slow down his growth, to act on the mechanism that makes malignant cells proliferate and medulloblastoma. Researchers from the Bambino Gesù pediatric hospital in Rome, in collaboration with the universities of Tor Vergata and Sapienza in Rome and Trento, discovered the mechanism that triggers the most aggressive form of this disease. Based on this discovery, the scholars have identified two medications potentially able to stop cancer growth and metastasis. The study, supported entirely by Airc, has just been published in the international scientific journal ‘Acta Neuropathologica’.
It affects 7 in a million children
Medulloblastoma has an incidence, in Italy, of about 7 children affected per million. The overall survival rate is currently 80% for ‘standard’ risk patients; unfortunately the figure drops to 30-60% for those at high risk. This tumor forms in the cerebellum, the area of the nervous system located at the base of the brain and responsible for controlling balance and coordination of movements. Medulloblastoma therapies involve surgical removal of the tumor, followed by radiotherapy and chemotherapy. The main obstacle to treatment, however, is the presence of cancer stem cells that are resistant to radium and chemo and have the ability to infiltrate and spread into the spinal cord of young patients. A new therapeutic route for this pediatric cancer, in particular for that of ‘Group 3’, the form with the highest risk of death (which occurs in more than 40% of cases within 5 years of diagnosis), comes from the results of the research conducted in the laboratories of the Child Jesus Oncohematology Area.
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I study
The investigation was coordinated by Franco Locatelli, director of Experimental and Precision Medicine and of the Oncohematology Area of the Holy See pediatric hospital, and by Francesco Cecconi, researcher of the Bambino Gesù and full professor at the University of Rome Tor Vergata. . The first author is Francesca Nazio, researcher of the Infant Jesus. The team of scientists has identified a new molecular mechanism, the alteration of which is responsible for the aggressiveness of medulloblastoma. In particular, it has been found that in Group 3 tumor the Amber1 protein is produced at excessive levels and, consequently, all the processes it regulates (autophagy and stem identity) function abnormally.
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Due to the overabundance of this protein, in fact, the mechanism used by the cells to get rid of the damaged components (autophagy) is strengthened and the cancer cells exploit this circumstance to survive and proliferate. Furthermore, the excess of Amber1 keeps the cells in a stem condition which on the one hand helps them to replicate faster, accumulating in the tissues of origin to form large tumor masses, and on the other hand helps them in their ability to migrate and form metastasis. Starting from these laboratory results, the researchers showed that the combination of two drugs (an autophagy inhibitor and a Stat3 stem factor inhibitor) blocks not only the growth of the tumor, but also its ability to produce metastases. .
The protein
The protein had already been identified by the same team of researchers of the Infant Jesus as a potent tumor suppressor in other pediatric and adult cancers, due to its direct role in cell cycle regulation. This step forward also proposes it as a very important target. “Many children already present metastases at the time of diagnosis, making it essential to develop more effective therapies – explains 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. “
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