Scientists at the Institut de Recherches Cliniques de Montréal (IRCM) discovered a mechanism that promotes the progression of medulloblastoma, the most common brain tumour found in children. The team found that a protein known as Sonic Hedgehog induces DNA damage, which causes the cancer to develop. This important breakthrough is published in the journal Developmental Cell.
Sonic Hedgehog belongs to a family of proteins that gives cells the information needed for the embryo to develop properly. It also plays a significant role in tumorigenesis, the process that transforms normal cells into cancer cells.
The team studied a protein called Boc, which is a receptor located on the cell surface that detects Sonic Hedgehog. The researchers had previously shown that Boc is important for the development of the cerebellum, the part of the brain where medulloblastoma arises, so they decided to further investigate its role.
With the current study the group found that the presence of Boc is required for Sonic Hedgehog to induce DNA damage. In fact, Boc causes DNA mutations in tumour cells, which promotes the progression of precancerous lesions into advanced medulloblastoma. The study shows that when Boc is inactivated, the number of tumours is reduced by 66 per cent. The inactivation of Boc therefore reduces the development of early medulloblastoma into advanced tumours.
Medulloblastoma ranks among the leading causes of cancer-related mortality in children. Current treatments include surgery, as well as radiation therapy and chemotherapy. Although the majority of children survive the treatment, radiation therapy damages normal brain cells in infants and toddlers and causes long-term harm.
As a result, many children who undergo these treatments suffer serious side effects including cognitive impairment and disorders. The results indicate that Boc could potentially be targeted to develop a new therapeutic approach that would stop the growth and progression of medulloblastoma and could reduce the adverse side effects of current treatments.