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SNO-SCIDOT Joint Conference on Therapeutic Delivery to the CNS

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SNO-SCIDOT Joint Conference on Therapeutic Delivery to the CNS

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2013 Pediatric Basic and Translational Research Conference Recap


The 2nd Biennial Pediatric Neuro-Oncology Basic and Translational Research Conference took place at the Hyatt Pier 66 Hotel in Fort Lauderdale.  The meeting was sponsored by the Pediatric Brain Tumor Foundation (PBTF), and organized by the Society for Neuro-Oncology (SNO).  More than 270 clinicians, scientists, research students, and post-doctoral fellows participated in the event.  There was representation from more than 15 countries with some of the more distant sites of origin being China, Australia, and Japan.


On the first day of the meeting, there were three Sunrise Sessions that probed the recent advances in translational therapeutics, optic pathway tumours in children, and radiation therapy for paediatric brain tumours.  The first scientific session was devoted to the topic of medulloblastoma in which there have been major strides made in our understanding of the basic science of this tumour.  Several presentations included further subgroup analysis within the four major subgroups for medulloblastoma — the WNT, the Sonic Hedgehog (SHH), Group 3 and Group 4 tumours.  There are data now to show that within any one of these subgroups, there are groups of patients who are doing better than others, and their risk for progression within these evolving subgroups is being better defined and calculated.  Several laboratories are using novel chemotherapeutics to target medulloblastoma based on known pathways of activation including the HGF/cMET, the SHH, and the WNT pathways.  In Session 2, there were presentations on novel paediatric brain tumour models including murine glioma formation with the KIAA1549:BRAF fusion gene; zebrafish models of CNS PNETs which recapitulate the pathology of the paediatric brain tumour; and a new genetic model of a choroid plexus tumor.  In Session 3, presentations on Ependymoma, High Grade Glioma and Therapeutics followed.  Here, it was demonstrated that ependymoma is a tumour with very few, if any, primary genetic alterations, but which has significant epigenetic alterations, making it a target for epigenetic therapy.  For high grade gliomas, there was great interest in the presentations on the role of the mutant histone H3.3 as a driver for this tumour type.  For translational therapeutics, some interesting targets included Wee1, KIAA1549:BRAF fusion gene anomaly, and the RAF/MEK/mTOR pathways.  The first day concluded with a session on stem cells, genetics/epigenetics and basic biology.   Here, there was an excellent presentation on the methylomic landscape of childhood medulloblastoma using molecular genetic techniques to comprehensively characterize the main features of DNA methylation in these tumours.


On the second day of the meeting, there were three more Sunrise Sessions on optimum therapy for craniopharyngioma, targeted therapies for paediatric brain tumours, and the epigenome of paediatric brain tumours.  The first scientific session was devoted to brainstem tumours, and in particular, the diffuse intrinsic pontine glioma (DIPG).  Perhaps here, more than anywhere, we were able to document significant progress since our last meeting in 2011.  Since the 2011 meeting, the H3.3-K27 and the H3.1-K27 mutations were identified, and found to specify subgroups of DIPG's.  The H3.3-K27 mutation in DIPG is associated with some other novel gene mutations, an increase in activation of the BMP and mTOR pathways, and a median overall survival of 17 months; whereas the H3.1-K27 mutation shows activation of PDGFR-alpha and p53, and has a median overall survival of only 11 months.  Throughout the day, there were additional sessions on medulloblastoma in which new targets for therapy were being pursued such as aurora kinase, various microRNA's, and myc.   We also learned of ongoing immunotherapy trials in children with PNET's and gliomas.  And, there was a presentation on a large cohort of patients from Japan whose germ cell tumours were studied using advanced genomic strategies.


In the short time span of two years, there have been several advances denoted in our understanding of medulloblastoma, ependymoma and DIPG's. Much of this work has been at the genomic characterization level which has depicted subgroups of patients for whom active and new therapeutic strategies are warranted.  These advances are in part attributed to the availability and accessibility of next generation sequencing technologies.  It is hoped that within the next two years, much more emphasis will be placed on translational therapeutic strategies which will benefit children with these aggressive cancers.  Some of these, no doubt, will be highlighted at the next biennial meeting of this group.


I should like to take this opportunity to thank Robin Boettcher, PBTF President and CEO, for the support of the Conference by the PBTF.  Special thanks are also given to Chas Haynes, Executive Director of SNO, and Linda Greer from SNO who helped enormously with the organization of this most highly successful conference.


James T Rutka, MD, PhD, FRCSC

Scientific Program Chair

Linda Greer
(281) 554-6589
(713) 583-1345
Author: Linda Greer
Phone: (281) 554-6589
Fax: (713) 583-1345
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