Aurora Kinase Inhibition in Neuroblastoma
Mentor: John Maris
Neuroblastoma is a pediatric cancer that arises from dysregulation during nervous system development. Due to the developmental nature of the disease, these children are commonly diagnosed within the first year of life. The genetics of neuroblastoma tumors largely varies and contributes to the severity of the disease. For example, patients with unfavorable genetics are classified as high risk and have a 5-year survival rate of less than 50%. Additionally, the survival after relapse is extremely rare, which underscores a need to develop effective treatment options for patients with high-risk neuroblastoma. New cancer treatment strategies include immunotherapy, which involves selectively delivering a chemotherapy agent to tumor cells based on cell-surface molecules that are expressed only on tumors. Some of the genetic changes that mark poor prognosis in neuroblastoma can upregulate certain cell-surface proteins. The Maris and Mossé labs have identified a protein called AURKA as a key target for new drug development. Eli-Lilly Pharmaceuticals has developed a very potent inhibitor of this protein that will enter a neuroblastoma clinical trial in the New Approaches to Neuroblastoma Therapy consortium very soon. Through a Crazy 8 initiative pilot project, the Maris and Mossé labs plan to collaborate to determine which is the best ‘partner’ drug for this new AURKA inhibitor, to plan ahead for the subsequent clinical trial, knowing that you do not cure cancer with single drugs alone. The POST student will work in the Maris Lab to perform these key experiments under the guidance of senior scientists from the Maris lab and adjacent Mossé lab. These data will be immediately translatable to neuroblastoma patients.