Kaat De Wever
Doctoral fellow – Pediatric Precision Oncology Lab Ghent – Center for Medical Genetics (UGent)
Principal investigator: prof. Kaat Durinck (PhD)
Research focus
Rhabdomyosarcoma is a rare and aggressive soft-tissue sarcoma, mostly affecting children and adolescents. Because of the high relapse rates observed in the patients and the difficulty of setting up large clinical drug testing trials, there is an urgent need for more targeted therapeutic entry points.
Aurora Kinase A (AURKA) has been described as a potential target in pediatric cancer treatment, including rhabdomyosarcoma in which it functions as an oncogene by stabilizing the PAX3-FOXO1 fusion protein and MYCN. However, since AURKA inhibitors have failed in clinical settings, PROTACs that trigger AURKA degradation and thereby inhibit not only kinase-dependent but also kinase-independent functions were developed in the lab.
In this research project, the efficacy and toxicity of those AURKA PROTACs will be investigated in vitro and in vivo using murine rhabdomyosarcoma models. Another objective of this study is to evaluate the AURKA PROTACs and inhibitors as novel entry points for potent combination therapies in pediatric sarcomas. Both type of drugs will be combined with a large library of FDA approved agents to discover compelling evidence of drug synergy. The drug combinations will be validated in both an in vitro and in vivo setting via multi omics readouts. Finally, rhabdomyosarcomas are considered as immunologically “cold”, however, we hypothesize that targeting AURKA might trigger anti-tumor immune responses. So AURKA inhibition and degradation will be evaluated as a possible entry point for immunomodulation using a rhabdomyosarcoma organoid-PBMC ex vivo co-culture systems.
Biography
In 2024, I obtained my Master’s degree in Biomedical Sciences (major in Cancer) at the University of Ghent. For my thesis, I performed my research on the optimization of 3D ex vivo cancer models in the Lab of Experimental Cancer Research and the Lab of Experimental Surgery.
Currently, I am a full-time doctoral fellow at the PPOL lab of Prof. Dr. Kaat Durinck, investigating AURKA degradation using PROTACs in rhabdomyosarcoma to test potential combination therapies and immunomodulation both in vitro and in vivo.
Contact & links
- Lab address: Center for Medical Genetics Ghent (CMGG), Medical Research Building 1 (MRB1), 2nd floor, office: 120.038, entrance 34, campus UZ Gent, Corneel Heymanslaan 10, 9000 Ghent, Belgium
- Pediatric Precision Oncology Lab Ghent
- Centre for Medical Genetics Ghent
- ORCID
- Kaat De Wever is interested to receive invitations for talks and presentations