Stem cell pathways and Notch signaling an emerging role in the development of acquired Drug Resistance in Neuroblastoma

Abstract

Abstract Purpose: Neuroblastoma 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 in addition to increased expression of genes linked to stem cell pathways. Methods: In this study we investigated 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 primarily in notch signalling, and stem cell development. Conclusions: The 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.