New research has pinpointed a key cause of metastasis from medulloblastomas, an aggressive childhood brain cancer.
Scientists from the University of Pittsburgh and the UPMC Children’s Hospital of Pittsburgh recently published a paper within Nature Cell Biology, explaining how medulloblastomas were able to replicate the skills of normal brain cells in early development, which was used to promote tumour spread. This new research could pave the way for new therapies and treatment options in the future.
What are medulloblastomas?
Although medulloblastomas are the most common malignant brain tumour within children, they are the leading cause of childhood cancer deaths. Treatment options for these tumour types usually involve surgery following by radiation and chemotherapy, with tumours that have not yet metastasized having the highest rates of long-term survival. However, up to one-third of sufferers will find that the tumour has metastasized or spread to other parts of the body, which significantly reduces the survival rate.
What did the research find?
There are many longstanding challenges which researchers have faced, including finding out how the tumours spread and how to stop potential metastasis. The team of researchers involved in this study used both patient and experimental mouse data to learn more about how medulloblastoma tumour cells metastasize, with the research highlighting the importance of a gene called SMARCD3.
Within metastatic tumours, the levels of SMARCD3 were much higher than medulloblastomas which had not spread. The team also studied the pathways that are usually used by healthy brain cells during early cerebellar development, which are shut off when the cerebellum matures. The findings showed that the gene was able to hijack and mimic these neurodevelopmental signalling pathways to encourage the spread of the tumour within children.
The scientists then targeted these pathways using the dastinib drug, an approved leukaemia treatment. Within mouse trials, the drug was able to preferentially kill the metastatic tumours which contained high levels of the SMARCD3 gene. As an approved drug, this research highlights the potential it could have when being used as a safe treatment for children with medulloblastoma metastasis tumours.
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