"You need Math1 for that pathway to give you medulloblastoma," said Zoghbi. "This shows that there is a connection between normal development and cancer and underscores how important it is to study developmental biology. Cancer, in this case, is normal development gone awry."

One additional part of the equation is Gli2, a gene that is required for the signaling pathway of sonic hedgehog. Zoghbi and collaborators showed that Gli2 is regulated by Math1, thus explaining how Math1 regulates the proliferation of the cerebellar granule neuron precursors.

"If you take away Math1, there is no proliferation," said Zoghbi. "If you take away Math1, but add Gli2, proliferation continues."

"Math1 sets the cell up to respond to external stimuli," said Flora. If the cell cannot respond to the stimulation, it does not proliferate.

That raises the question of whether removing or inactivating Math1 might work as a treatment. That could depend on the stage of the brain's development, Flora said.

Most medulloblastomas arise after the age at which most of the cerebellar structure is complete. At that time, Math1 should be less active or even inactive in that structure.

"At least in theory, you could target these developmental pathways to at least slow down the growth of the tumor without impairing brain function," said Flora.

Source: Baylor College of Medicine