Pediatric Brain Cancer Cells Killed by Enzyme Blockade

Inhibiting heparanase observed to inhibit medulloblastoma cells.

Blocking an enzyme that is crucial to the cellular microenvironment was observed to inhibit the growth of brain cancer cells, according to a study published by Molecular Cancer Therapeutics.

While leukemia is the most common pediatric cancer, brain tumors account for 25% of childhood cancers. Several types of childhood cancers are curable, including medulloblastoma, a cancer of the cerebellum; however, medulloblastoma has a cure rate of approximately 50% in this population.

While medulloblastoma is curable, it is known to metastasize within the brain, which can result in recurrent disease even after surgery. This occurrence highlights the need for new treatment options, according to the study.

The authors focused on proteoglycans, molecules that are found in the brain and have 1 or more attached carbohydrate chains. The enzyme heparanase is needed to degrade the chains.

The authors found that medulloblastoma cells require heparanase to survive and duplicate. The authors believe that this may be a new and effective approach to treating the disease.

"Cancer cells invade the normal brain, which makes them difficult to treat. During this invasion, the tumor cells break down the proteoglycans that are found on and between the cells. When we blocked the enzyme heparanase, that degrades proteoglycans, it stopped the growth of the tumor cells,” said lead researcher Karin Forsberg Nilsson, PhD.

The investigators found significantly higher levels of heparanase in pediatric brain tumors compared with healthy brains.

The authors discovered a molecule that inhibits the enzyme and results in medulloblastoma cell death, according to the study. Importantly, healthy brain cells were not affected by the therapy, making it an ideal candidate for treatment in pediatric patients.

In mice, the heparanase inhibitor was observed to shrink the tumors up to 80%, according to the study.

While the findings are still early, they suggest that blocking heparanase could provide pediatric patients with a more effective treatment.

"The study increases our knowledge of how cancer cells interact with the tumor microenvironment. We hope that this can be of use for new therapies,” said first author Argyris Spyrou.