Medulloblastoma: a disease with disorganized developmental signaling cascades.

Sonic Hedgehog, Wnt and PI3K/Akt are three developmental signalling cascades that all have crucial functions during normal brain development. The activation of one or several of these cascades is also found in the majority of medulloblastoma, the most common pediatric malignant tumor of the central nervous system. The aberrant expression of key molecules in developmental signalling pathways or inhibition of the activity of proteins regulating the activity of these cascades is important for medulloblastoma proliferation and survival. These developmental signal transduction pathways transfer signals from the cell membrane to transcription factors in the nucleus, resulting in an altered gene expression. Molecular cross-talks between these developmental cascades have been described in several cancers and may have important functions in tumorigenesis. One common kinase for these three signalling cascades is GSK-3β, which seems to be the glue that links these cascades together. Medulloblastoma cells display many characteristics that are interrelated to the progenitor cells of the embryonic brain where these developmental cascades are essential for proper development. Hence, understanding the relationship between normal brain development and medulloblastoma molecular pathogenesis is essential for more efficient, less toxic tailored therapies to be developed and implemented.