Doctoral fellow - Lab for Pediatric Oncogenomics, Center for Medical Genetics (Faculty of Medicine and Health Sciences, UGent)
Principal investigator: prof. Frank Speleman (PhD)
Neuroblastoma (NB) is the most common extracranial solid tumor in children characterized by poor overall survival rates. The tumor arises from neural crest cells during early embryonic development due to the deregulation of signaling pathways important for the development of the peripheral nervous system. Considering that NB is a childhood cancer, it is of utmost importance that we look for more targeted therapies which are associated with higher efficiencies and reduced toxicities.
Importantly, in a tumor entity like NB characterized by a low mutational burden, the number of druggable genes for targeted therapy is limited. Interestingly though, translational addiction is now becoming recognized as a significant mechanism for cancer cells to upregulate non-mutated replicative stress-resistor genes, to which they become dependent for survival. With regards to NB, many of the candidate dependency genes are functionally connected to the Aurora Kinase A enzyme, highlighting the potential of the latter as a novel therapeutic target in NB.
Throughout the course of my doctorate, I will be investigating selective Aurora Kinase A inhibition as a novel entry point to identify synthetic lethality targets in NB. In addition, I will explore the use of combined pharmacological inhibition together with protein degradation using a new and exciting class of drugs (PROTACs) as an innovative therapeutic approach in NB. Overall, my research aims to uncover a deeper understanding of the molecular aspects driving NB tumorigenesis and provide a boost in the search for novel targeted therapies for this potentially fatal childhood cancer.