MYC-driven medulloblastoma

Medulloblastoma and neuroblastoma exemplify the current embryonal tumor model. Sonic hedgehog signaling (SHH signaling pathway) is required for cerebellar development and its dysregulation is implicated in formation of medulloblastoma.

The transcription factor Mycn orchestrates proliferation and differentiation of the developing peripheral neural crest.

Amplification of the MYCN gene is the predominant marker for aggressive neuroblastoma, and correlates with poor prognosis.

Current evidence suggests that Mycn is also the primary executor of Sonic hedgehog signaling in the cerebellum and that the Sonic hedgehog pathway regulates levels of both MYCN mRNA and Mycn protein product independently.

Destabilization of Myc through inhibition of phosphoinositide 3-kinase signaling (PI3K signaling pathway) exhibits promise not only in medulloblastoma and neuroblastoma, but in a wide range of Myc-driven tumors.

References

 An Animal Model of MYC-Driven Medulloblastoma . Pei, Y., Moore, C., Wang, J., Tewari, A., Eroshkin, A., Cho, Y., Witt, H., Korshunov, A., Read, T., Sun, J., Schmitt, E., Miller, C., Buckley, A., McLendon, R., Westbrook, T., Northcott, P., Taylor, M., Pfister, S., Febbo, P., & Wechsler-Reya, R. (2012). Cancer Cell, 21 (2), 155-167.