From Neurons to Neuroblastoma
During development the sympathetic branch of the nervous system is assembled by the differentiation of immature neurons (neuroblasts) into mature sympathetic neurons. In rare cases this process does not happen correctly and the cells become cancerous. This type of cancer is called a Neuroblastoma that occurs almost exclusively in babies and children. Neuroblastoma is the most common solid tumor that occurs outside the brain in infants and children and it is responsible for 15% of childhood cancer deaths. Although the survival rates are good for some patients, those children diagnosed with high-risk neuroblastoma have survival rates as low as 35%. Moreover relapses are common and these relapses are often treatment resistant. For this reason neuroblastoma remains a significant clinical challenge and the development of novel treatment strategies is essential.
Given that there is widespread epigenetic dysregulation in neuroblastoma, treating with drugs that target the epigenome holds promise as a therapeutic approach. In recent years, histone deacetylase (HDAC) inhibitors, which cause selective activation of gene expression, have been shown to be potent chemotherapeutics for the treatment of a wide range of cancers. However while these drugs have been extensively studied in cancers affecting adults, information is lacking on their potential in neuroblastoma. In a new study we examined the ability of the FDA-approved drug Romidepsin, a selective HDAC1/2 inhibitor, to act as a cytotoxic agent in neuroblastoma cells. We reported that treatment with Romidepsin induced neuroblastoma cell death through caspase-dependent apoptosis. Romidepsin was also more potent in treatment of neuroblastoma cells which had emplification of the MYCN gene, which is an important prognostic marker of poor survival. This study shows that Romidepsin may be a promising candidate for further study in the treatment of neuroblastoma in infants and children.
http://www.sciencedirect.com/science/article/pii/S0304394017304135
Authors: Ger O'Keeffe, Shane Hegarty and Katie Togher.
This article first appeared on The O'Keeffe Lab blog website as part of their ‘Project updates and Outreach’. See original article below:
http://www.okeeffelab.com/single-post/2017/05/17/From-Neurons-to-Neuroblastoma