Novel Inhibitors against Neuroblastoma

Neuroblastoma is one of the most common cancers in children up to one year of age. Neuroblastomas develop when certain nerve cells degenerate and form sizable lumps – in most cases in the abdomen of the child. About 130 cases of the disease are diagnosed each year in Germany.

In contrast to many other types of cancer, neuroblastomas sometimes heal spontaneously. In most patients, this type of cancer can be easily treated with conventional drugs. However, the chances of recovery and survival are slim in 20 percent of the cases. The reason: The tumors form metastases that don't much respond to conventional drugs.

Why the tumor becomes aggressive

“The most important factor for a poor prognosis is an amplification of the MYCN gene,” says Professor Martin Eilers at the Biocenter of the University of Würzburg. This leads to an increased production of the MYCN protein, which is assumed to be responsible for the aggressive growth and the resistance to therapy of the tumors.

The MYCN protein stimulates cell growth. In normal cells, it can only be active for a short while, because it is quickly degraded. The situation is different in neuroblastomas: There, the protein is protected from fast degradation, because it is bound to a partner protein (Aurora-A). This was shown by Martin Eilers' study group in 2009.

How the novel inhibitors work

Together with an international team, the Würzburg study group has now made further progress in this research: They identified novel inhibitors that are able to disrupt the complex of Aurora-A and MYCN. If aggressive neuroblastomas are treated with these inhibitors, they cease to grow. At least, this is the result of tests in a mouse model.
“This might show the way to the development of new and better drugs against this aggressive tumor,” says Eilers. According to the professor, other long-known inhibitors of the Aurora-A protein are already being tested in the first clinical trials in the USA.

The inhibitors of Aurora-A are promising for the treatment of other types of cancer as well: The fatal complex of Aurora-A and the MYCN protein is also present in particularly aggressive prostate carcinomas.

“Small Molecule Inhibitors of Aurora-A Induce Proteasomal Degradation of N-Myc in Childhood Neuroblastoma”, Markus Brockmann, Evon Poon, Teeara Berry, Anne Carstensen, Hedwig E. Deubzer, Lukas Rycak, Yann Jamin, Khin Thway, Simon P. Robinson, Frederik Roels, Olaf Witt, Matthias Fischer, Louis Chesler, Martin Eilers, Cancer Cell, 20 June 2013, DOI 10.1016/j.ccr.2013.05.005

Contact person

Prof. Dr. Martin Eilers, Biocenter at the University of Würzburg, T +49 (0)931 888-4442, martin.eilers@biozentrum.uni-wuerzburg.de