MYC-driven medulloblastoma (MB) is an aggressive form of childhood brain cancer that develops from neural stem cells in the cerebellum- an area of the brain at the back of the head that helps motor coordination, balance, and posture.
MYC is the name of a group of genes often linked to the formation of cancers, including MB. MB has now surpassed leukemia as the most fatal childhood illness, with 30% of cases not responding to available treatments.
For the present study, the researchers sought to find a novel target for treating MYC-driven MB. From genetic screening and metabolomic profiling data, they identified dihydroorotate dehydrogenase (DHODH) as a potential target to treating MYC-driven MB. DHODH is an enzyme involved in building nucleotides- or DNA blocks- in the human body.
To test the potential new target, the researchers blocked DHODH on mouse models of MYC-driven MB, and compared them to controls. They found that blocking DHODH halted cancer growth, and left surrounding brain and nerve cells intact- one of the key challenges to existing treatments, including surgery, radiotherapy, and chemotherapy, which are linked to multiple side effects.
"This potential treatment pathway will allow us to kill the weeds but save the flower of the developing brain," said first author of the study, William Gwynne, a post-doctoral researcher of the Centre for Discovery in Cancer Research, in a press release.
"This DHODH treatment target is full of promise, but it will take several years before we can reach the clinical trial stage. This potential new treatment, unlike current ones, will not be toxic to the developing brain,” he concluded.
Sources: ScienceDirect, Cancer Cell
