Researchers, in a McMaster University-led
study, discovered that by blocking the production of an enzyme called DHODH,
they were able to halt the growth of MYC gene-amplified medulloblastoma in
mouse models, the most aggressive subtype of this cancer.
An enzyme that drives the growth of an
often-lethal childhood brain cancer may hold the key to a future treatment, the
study said.
Common medulloblastoma symptoms include gait
and balance difficulties, nausea, headaches and swelling of the head.
By the time children are diagnosed, the cancer
has often spread throughout the brain and into their spinal fluid, especially
if it is the MYC-amplified subtype.
First author William Gwynne said that while
blocking DHODH stops the cancer spreading, healthy brain and nerve cells are
spared. This will avoid the after-effects of current treatments, including
radiotherapy and chemotherapy, which can impair children’s brain development
even if their cancer is successfully treated.
“This potential treatment pathway will allow
us to kill the weeds but save the flower of the developing brain,” said Gwynne,
a post-doctoral researcher of the Centre for Discovery in Cancer Research
“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.”
The study was published in the journal Cancer
Cell on Nov. 10.
Gwynne said all types of medulloblastoma
originate from neural stem cells in the cerebellum, the part of the brain that
controls voluntary actions such as walking, balance, co-ordination and speech.
The cerebellum develops fully after a child is born.
He said the cancer starts when cell
development in the cerebellum goes awry but studying the causes of this
dysfunction can lead to new treatments.
Gwynne said that medulloblastoma is the most
common pediatric brain cancer diagnosed in children and brain tumors have
recently overtaken leukemia as the most lethal childhood malignancy.
“Over the last two decades, we have made
significant treatment advances in surgery, chemotherapy and radiotherapy, so
the five-year survival rate for medulloblastoma is now more than 70 per cent,”
said Gwynne.
“However, the roughly 30 per cent of children
whose cancer does not respond to currently available treatments have no other
options.”
Reference:
William Gwynne
et al, Cancer-selective metabolic vulnerabilities in MYC-amplified
medulloblastoma, Cancer Cell, DOI 10.1016/j.ccell.2022.10.009