Abstract
Neuroblastoma (NB) is a highly malignant solid tumor in children that is responsible for more than 15% of all paediatric cancer-related deaths. Currently there is no effective cure for high-risk NB, and the survival rate of relapsed/refractory patients is very low. MYCN gene amplification in NB is associated with advanced stage disease, rapid tumor progression, poor prognosis, and resistance to therapy. Ornithine decarboxylase (ODC) is a rate-limiting enzyme that controls the biosynthesis of polyamines and both ODC and polyamine levels are often elevated in cancer. Since ODC is a transcriptional target of MYCN, the polyamine pathway presents an attractive target for therapeutic intervention in NB. The compelling preclinical effectiveness of the ODC inhibitor α-difluoromethylornithine (DFMO) combined with its high safety profile has provided the rationale to advance this drug to the clinic and a FDA-approved Phase I NB clinical trial with DFMO alone and combined with etoposide is currently underway. Given the current lack of effective therapies, the identification of novel and innovative combination therapies is paramount in the endeavour to combat this aggressive paediatric malignancy.
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Acknowledgment
The authors would like to thank Dr. David J. Feith (Pennsylvania State University College of Medicine) for helpful comments and critical review of the manuscript. The authors would like to sincerely apologize to all colleagues in the field for omitting many of their important literature contributions that pertain to this book chapter, due to a set limit in allowable references.
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Bachmann, A.S., Geerts, D., Saulnier Sholler, G.L. (2012). Neuroblastoma: Ornithine Decarboxylase and Polyamines are Novel Targets for Therapeutic Intervention. In: Hayat, M. (eds) Neuroblastoma. Pediatric Cancer, vol 1. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-2418-1_9
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