An international and multidisciplinary team of researchers, clinicians, and data scientists have been awarded a Sinergia grant from the Swiss National Science Foundation (SNSF) to improve treatment for children with aggressive brain tumours.
The new Sinergia consortium involves principal investigators from the DMG/DIPG Center Zurich, at University Children's Hospital, the ETH Zurich, and the Centre for Molecular Medicine Norway (NCMM) and aims to harness novel technologies for precision medicine in pediatric diffuse midline glioma (DMG) and diffuse intrinsic pontine glioma (DIPG).
DMG currently has a poor survival rate and, to date, no effective treatment
DMG/DIPG is an aggressive brain tumour that primarily affects children but can also affect adults. The survival time for patients is poor, with over 90% of DMG/DIPG patients dying within two years of their diagnosis. Whilst significant progress has been made in recent years in better understanding the molecular biology of DIPG/DMG, there has been a lack of similar advancements in finding novel and effective drugs or combinations of drugs.
The Sinergia consortium received CHF 3.1 million for a research project to discover therapeutic vulnerabilities in patient-derived preclinical DMG models, and to utilize a drug repurposing strategy whereby thousands of approved and investigational drugs are tested for anticancer activity. Each research group will contribute their expertise to address the main project goal of using novel technologies for molecular characterization of DMGs, rapid discovery and validation of effective and safe drugs, and the discovery of biomarkers of drug sensitivity.
Dr. Javad Nazarian, Head of the Translational Research Program of the DIPG/DMG Center, at University Children's Hospital Zurich and Lead of the Sinergia consortium, will perform high-throughput drug screening using 30 patient-derived DMG models and thousands of drugs that have so far not been investigated in preclinical DMG studies. The DIPG/DMG Center will use this opportunity to harvest novel technologies to discover therapeutic vulnerabilities in patient-derived preclinical DMG models and utilize a drug repurposing strategy whereby thousands of approved and investigational drugs are tested for anticancer activity.
Dr. Sebastian Waszak, Head of the Computational Oncology Group at NCMM, will characterize the genomic and the epigenomic landscape of preclinical DMG models and develop a computational drug repurposing strategy for DMG/DIPGs.
Prof. Fatih Yanik, Head of the Neurotechnology Group at the ETH Zurich, will develop a novel minimally invasive brain network measurement technology that will allow the team to assess neurotoxicity of drugs and drug combinations.
Other project partners include Prof. Adriano Aguzzi (University Hospital Zurich), Prof. Stephan Neuhauss (University of Zurich), Dr. Pan Pantziarka (Anticancer Fund), Dr. Anton Yuryev and Dr. Jabe Wilson (Elsevier Life Sciences Professional Services), Mr. Finlay MacLean (formerly at Elsevier), and the Children’s Brain Tumor Network. Sabine Mueller, MD PhD MAS (University of California, San Francisco) as an expert neuro-oncologist will contribute to the translation of the project results to clinical studies.
Study will have an impact on how clinical trials are designed, helping to improve outcomes for patients
The Sinergia consortium hopes that this project will have a major impact on the design of future clinical trials and, thus, help to improve outcomes for children diagnosed with DMG.
Dr. Javad Nazarian comments: "We are honoured to be the recipient of one of the largest government grants in support of a deadly childhood brain cancer. DIPG/DMG is a devastating and challenging pediatric disease and it will take a multidisciplinary team to tackle the problem. We thank the SNSF for supporting us and we look forward to establishing effective therapies for this patient population."
Dr. Sebastian Waszak adds: "This consortium will allow us to develop a genome-based approach to drug repurposing and hopefully, in the near future, will improve precision medicine-based therapies for children with diffuse midline glioma.”
The Anticancer Fund, which played a key role in the initiation of this collaboration, welcomes the news. According to Dr Pan Pantziarka: “This type of multi-disciplinary, focused project promises to make great strides in developing the next generation of drug repurposing. We believe it will be a model with wide application to other cancers with few therapeutic options.”
Further information
For more information, please contact Dr. Javad Nazarian (Javad.Nazarian@kispi.uzh.ch) or Dr. Sebastian Waszak (waszak@ncmm.uio.no).