“Efficacy and safety of ch14.18/CHO in neuroblastoma”
by Holger N. Lode, MD
Presenter: Holger Lode, MD
Professor and Chair of Pediatrics
University Medicine Greifswald
The study of epigenetic deregulation of cancer cells has moved to the forefront of cancer research as a result of the recent discovery that across all tumor entities roughly 20% of all mutations affect genes implicated in processes controlling methylation and chromatin modification. At the same time, an increasing number of novel epigenetic drugs are emerging and going through in vitro, pre-clinical and clinical testing. CRISPR/Cas technology has revolutionized controlled genome editing offering new exciting possibilities to investigate the complex epigenetic control of gene expression in cancer cells even down to the single cell level. In this workshop we bring together experts in this field explaining how new insights into the highly complex epigenetic regulatory processes can provide deeper understanding of tumor initiation, progression and therapy resistance and how genome editing can aid to further fuel this discovery process, ultimately providing us the tools and data to identify novel drug targets and therapeutic strategies to combat neuroblastoma.
Much of the pre-clinical and clinical research on neuroblastoma is aimed at discovering more effective therapy for the majority of children who present with clinically advanced disease. Even successful current therapy for advanced neuroblastoma can lead to severe short and longterm side-effects, indicating the need for improved treatment strategies. Recent advances in organic chemistry and structure-aided design have seen a marked increase in the number of available targeted anticancer drugs, but the relative rarity of neuroblastoma may mean that novel trial designs are required to more rapidly incorporate pre-clinical advances into frontline protocols. This significant shift, coupled with more sophisticated methods of minimal residual disease monitoring, techniques for detailed analysis of tumor heterogeneity and ‘window therapy’ trial designs used to assess treatment efficacy in real-time, suggest that traditional single comparison phase 3 trial designs may no longer be suited to the problem of incorporating promising single agent or combination therapies into the treatment of newly diagnosed patients. The advent of precision or personalised oncologic medicine, aimed at better matching the treatment to the target holds the promise of improved cure rates and lower side-effect profiles. However, the relatively low number of genomic targets in neuroblastoma and the poor availability of novel agents for paediatric patients, means the field faces significant clinical research challenges in the future. We have asked the leaders of frontline international Phase 3 clinical trials for advanced neuroblastoma and early phase trialists to debate the following hypothesis: “That a conventional single comparison, randomised, Phase 3 trial design is no longer appropriate for newly diagnosed advanced neuroblastoma patients”.