New research pinpoints a key cause of metastasis from an aggressive form of brain cancer in children and provides a potential new therapy for treating these tumors in the future.
In a paper, published in Nature Cell Biology, physician-scientists discovered that medulloblastomas hijack a skill that normal brain cells use during their early development and then manipulate it to help tumors spread.
“Children with medulloblastomas that have not yet metastasized may have a high likelihood of long-term survival, but if those tumors have spread, the survival rate is significantly reduced,” said the senior author. “Longstanding challenges that we face in the field include understanding how tumors are able to spread and how we can stop tumor metastasis.”
Brain tumors are the leading cause of cancer death in children. The most common malignant children’s brain tumor is medulloblastoma, which form in a region of the brain called the cerebellum, with about 500 new cases diagnosed in the U.S. each year. Medulloblastomas are commonly treated with surgery followed by radiation and chemotherapy, but in up to one-third of children, the tumor will metastasize, or spread out to tissues and organs beyond where the tumor originated. When tumor cells spread, treatments no longer work and the outcomes are grim.
To learn how medulloblastoma cells metastasize, the team leveraged patient and experimental mouse data. They found that levels of a gene called SMARCD3 were significantly higher in metastatic tumors compared to those that had not spread.
They also showed that SMARCD3 hijacks neurodevelopmental signaling pathways to promote tumor cell spreading. These pathways are used by healthy brain cells during early cerebellar development and are shut off when the cerebellum matures.
Next, the researchers targeted these pathways with a drug called dasatinib, which has been approved to treat leukemia in the clinic. In a mouse model of medullobastoma, dasatinib preferentially killed metastatic tumors with higher levels of SMARCD3, suggesting that the drug causes little or no harm to normal brain cells and could be safe for treating patients with medulloblastoma metastasis.
“We’ve been thinking of medulloblastoma metastasis from the perspective of neuroscience and understanding how abnormal brain development causes and influences brain tumors,” said the author. “This approach helped us to pinpoint fundamental mechanisms of medulloblastoma metastasis, which will help us develop safe, effective and personalized treatments for children with this devastating brain cancer.”
https://www.nature.com/articles/s41556-023-01093-0
http://sciencemission.com/site/index.php?page=news&type=view&id=publications%2Fa-neurodevelopmental&filter=22
Key culprit behind pediatric brain cancer metastasis
- 729 views
- Added
Latest News
How Botox enters the brain…
By newseditor
Posted 04 Jun
Gut microbiome changes link…
By newseditor
Posted 04 Jun
Artificial intelligence sys…
By newseditor
Posted 03 Jun
Deep-brain stimulation duri…
By newseditor
Posted 03 Jun
RNA-guided mechanisms drivi…
By newseditor
Posted 03 Jun
Other Top Stories
Mood stabilizer, lithium, increases life span in fruit flies
Read more
Drug used for rare disease may be able to treat heart disease
Read more
Normal striatal uptake in Huntington disease mouse models
Read more
New insights into how the brain adapts to stress
Read more
First scans show how the LSD drug affects the brain
Read more
Protocols
Optical opening of the bloo…
By newseditor
Posted 04 Jun
Protocol to establish a gen…
By newseditor
Posted 03 Jun
Metaboverse enables automat…
By newseditor
Posted 02 Jun
Ratphones: An Affordable To…
By newseditor
Posted 31 May
BigNeuron: A resource to be…
By newseditor
Posted 29 May
Publications
Presynaptic targeting of bo…
By newseditor
Posted 04 Jun
Sleep is required to consol…
By newseditor
Posted 04 Jun
The effects of caloric rest…
By newseditor
Posted 04 Jun
Nuclear lamina erosion-indu…
By newseditor
Posted 04 Jun
Augmenting hippocampal-pref…
By newseditor
Posted 03 Jun
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 10 Mar
ASCO-2020-GYNECOLOGIC CANCER
By newseditor
Posted 10 Mar