Fredrik Swartling

Project summary

New ways to understand how brain tumours develop and how they can be treated

MYCN belongs to the MYC family of proteins, which are implicated in at least half of all cancers. We study MYCN because it is strongly associated with brain tumours in both children and adults that have a very poor prognosis. The MYCN protein is required during brain development, but has a very short half-life and is therefore rapidly degraded in normal cells.

 

The research project has discovered how MYCN escapes degradation and becomes stabilised during the development of brain tumours. In patients with brain tumours, we have identified mutations – genetic alterations – in FBW7, an enzyme that regulates the stability of MYCN.

 

The study first aims to identify the normal cell type from which these brain tumours originate. Using different models as well as tumour cells cultured from patients, we aim to investigate how MYCN is stabilised and to identify other proteins that interact with MYCN in the tumour. To prevent brain tumours from developing, we need to understand which steps are required and the order in which they occur.

 

The study has recently identified two compounds with potential applications in cancer treatment. One inhibits the regulation of MYCN itself, while the other inhibits its stabilisation. The research project aims to explain how MYCN becomes stabilised, demonstrate how MYCN drives tumour development, and determine whether the newly identified compounds could become potential drugs for the future treatment of these aggressive and difficult-to-treat brain tumours.