Investigating the role of the MYCN-CDCA2 axis in neuroblastoma

Neuroblastoma is a cancer originating from the peripheral nervous system (the nerves and ganglia -neuron cell bodies – outside of the brain and spinal cord) affecting infants and very young children. Although the major chemical changes in the body occurring in neuroblastoma have been discovered, clinicians and researchers are still struggling to find ways to prevent tumour growth, especially the neuroblastoma-causing gene called MYCN. An abnormal increase of MYCN, consequence of a disease-causing process called gene amplification (where a specific gene is copied multiple times, disproportionately as to other genes), has been identified as the most important molecular alteration in neuroblastoma.

Unfortunately, no laboratory has been successful, at least so far, in developing a drug that blocks MYCN cancerous activity. In our laboratory, we have recently identified a link between MYCN, and another molecule frequently observed to be at increased levels in cancer CDCA2 (also called Repo-Man). In this proposal, we would like to validate a new therapeutic strategy for neuroblastoma based on the development of a molecular inhibitor of CDAC2 (creating a treatment that prevents CDAC2 from working as it usually would).

In preliminary experiments, we have gathered evidence suggesting that a CDCA2 blocking protein inhibits the proliferation of cancer cells containing MYCN (so it is possible that using a protein to inhibit CDCA2 may limit the growth of cancer. Since alterations of MYCN are common in other childhood malignancies (cancers) of the nervous system, such as medulloblastoma and glioblastoma, this study could pave the way to new therapeutic avenues for children with many types of cancer.

Grant Award – Fellowship 2019-2022

Funding Award – £71,000

Funding Awarded to – Professor Paola Vagnarelli

Research Location – Brunel University

Lead Researcher – Professor Paola Vagnarelli

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