- Universität Zürich > Medizinische Fakultät > Kinderspital Zürich > Onkologie, Abteilung > Prof. Dr. Felix Niggli
- Niggli
Current Research Project
- Title / Titel
- Innovative treatment approaches for Ewing's sarcoma
- Summary / Zusammenfassung
- Ewing’s sarcoma comprises a family of tumors affecting bone and soft tissue in adolescence. Despite significant advances in prognosis in the last decades, optimization of currently available treatment options have now reached a plateau. Therefore, there is an urgent need to develop novel treatment strategies and to identify therapeutic targets.
One of the key features of the great majority of Ewing’s tumors is the expression of chimaeric translocation products comprised of the EWS gene and a member of the ets gene family of transcription factors. Expression of these fusion proteins is well studied and it is now established that they have a key role in both development as well as maintenance of Ewing’s tumors, most likely through inadequate regulation of target genes. Because of this pivotal role, the fusion proteins would represent ideal therapeutic targets. However, as they represent transcription factors, they can so far not be directly targeted by promising small molecules and therapeutic efforts have focused more on gene therapy approaches whose clinical application awaits further development. Interestingly, we recently identified a small molecule kinase inhibitor which induces apoptosis and reduces the transcriptional activity of the most prevalent Ewing’s fusion protein, EWS/FLI1. We will further characterize the anti-tumor effect of this molecule both in vitro as well as in vivo, identify posttranslational modifications in EWS/FLI1 with special emphasis on phosphorylations and identify signal transduction pathway(s) important for modulating the activity of EWS/FLI1.
The project will contribute to the development of novel treatment strategies for Ewing’s sarcoma, but will also provide mechanistic insights into the signal transduction pathway(s) important for development of this tumor.
- Keywords / Suchbegriffe
- Ewing's sarcoma, EWS/FLI1, post-translational modification, siRNA screen, kinase inhibitors
- Project Leadership and Contacts /
Projektleitung und Kontakte Prof. Felix Niggli (Project Leader) felix.niggli@kispi.uzh.ch Prof. Beat Schäfer
- Funding Source(s) /
Unterstützt durch - SNF (Personen- und Projektförderung)
- Duration of Project / Projektdauer
- Mar 2008 to Feb 2011