In a study published in the journal Nature Medicine, an international research team discovered a new molecular pathway that triggers aggressive medulloblastoma. They also discovered an antidepressant drug (Rolipram) based on this new Its molecular pathway is the target to combat this most common malignant childhood brain tumor.
"Neuroblastoma has different molecular subtypes and cellular origins." At present, there are few research results on gene mutations related to medulloblastoma formation. In this study, the scientists identified a gene that encodes Gas (a type of G protein)-GNAS. GNAS is an effective tumor suppressor gene, knocking it out can form a mouse model of medulloblastoma.
The researchers claim that the mouse model they invented can form a more targeted and effective molecular therapy approach, which greatly reduces the harmful effects of currently commonly used cancer therapies (chemotherapy, radiotherapy or surgery) .
After the mouse model was determined, the scientists used Rolipram, an antidepressant drug that has been approved in Europe and Japan, to treat medulloblastoma mice. They found that Rolipram increased cAMP levels in mice, and cAMP repaired GNAS. -Tumor inhibitory effect of Gas pathway, so that the tumor shrinks and finally disappears.
In addition, the researchers also found that the formation of aggressive medulloblastoma is related to a protein called Sonic hedgehog, which is one of the most important molecules in the formation and development of tissues. The increase in intracellular cAMP levels also enhances the activity of Sonic hedgehog inhibitors.
The researchers wrote in the article: "This study identified the unprecedented tumor suppressor function of Gαs, indicating that G protein regulation can be used as a potential therapeutic approach." The scientists also stated that the application of the research results to clinical trials is also A lot of work needs to be done, and it often takes a long process from mouse experiment to clinical application.
About medulloblastoma
medulloblastoma is a highly malignant primary brain tumor that arises in the cerebellum and posterior fossa. It was originally mistaken for medulloblastoma to be glioma, but now it is generally believed to belong to the family of primitive neuroectodermal tumors (PNET).
PNET is histologically similar to cerebellar medulloblastoma, and like cerebellar medulloblastoma, it is derived from undifferentiated precursor cells of neuroepithelial cells. Patients often have symptoms of increased intracranial pressure as their first symptoms, such as headache and vomiting.