New epigenetic therapy for high-risk neuroblastoma (MIRNATHERAPYNBL)
New epigenetic therapy for high-risk neuroblastoma
Date du début: 1 oct. 2013,
Date de fin: 30 sept. 2017
Neuroblastoma (NBL) is the most common solid tumor of infancy. Nearly 45% of all children with NBL are designated as high-risk patients and 60% of them die. Therefore, there is an urgent need to identify and target the molecular programs that are responsible for NBL aggressiveness, especially those that contribute to metastasis and resistance to chemotherapy.Recently, it has become evident that microRNAs (miRNAs) are deregulated in numerous diseases including cancer. Particularly in NBL, there is a global reduction of miRNA levels, especially in high-risk patients, and the expression of miRNA processing machinery components (i.e. Drosha, Dicer) impact on patient outcome. MiRNA restoration can be the basis for novel forms of therapy, by limiting the metastatic potential of NBL tumor cells and/or enhancing their sensitivity to current forms of treatment.The overall goal of my research will be to restore the levels of miRNA using a full miRNA library (1200 miRNAs) in highly chemoresistant NBL cells, and monitor the response with the miRNA alone or in combination with currently used chemotherapy drugs. The effect of the miRNA(s) will be validated in a expanded panel of NBL cell lines. Furthermore, we plan to develop a therapeutic tool based on nanoparticles, to target NBL cells in vivo and overexpress the target miRNA.Finally, the levels of those miRNA are going to be evaluated retrospectively in FFPE archived samples, in order to determine if the expression of a particular miRNA (or a signature) can be a biomarker of disease, indicator of minimal-residual disease or response to therapy and, correlation with overall or post-recurrence survival.
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