Stem Cell Pathways and Notch Signalling an Emerging Role in the Development of Acquired Drug Resistance in Neuroblastoma

Abstract

BackgroundNeuroblastoma is a paediatric tumour that develops from embryonal neural crest cells that give rise to the sympathetic nervous system. Aggressive high-risk disease remains a clinical challenge and despite multi-modal therapy, survival rates are poor. Most neuroblastomas initially respond well to induction chemotherapy however, 50-60% of patients with high risk disease will relapse with aggressive disease. A major obstacle in the successful treatment of this disease is the development of acquired resistance to chemotherapeutic agents. We hypothesize that aggressive neuroblastomas acquire a more immature phenotype and an increase in expression stem cell related genes. MethodsThis study investigates the role of stem cell related genes in the development of acquired drug resistance using Q- Real Time PCR and bioinformatics analysis on three-paired vincristine sensitive and resistant cell lines. Results: The study outlines 11 differentially expressed genes with several targets involved in stem cell development, differentiation and the notch signalling pathway. ConclusionsThe findings implicated in this study, which include comparative analysis against patient microarray data, warrants further study on the functional effects of these genes/pathways to elucidate their role in acquired drug resistance.