CRUK Children's Brain Tumour Centre of Excellence 2024

Almost no new treatments of childhood brain tumours have been developed in over 50-years: these diseases continue to kill more children than any other cancer.

Therefore, in 2018 we established the CRUK Children’s Brain Tumour Centre of Excellence (CRUK-CBTCE) with a vision to cure all children with a brain tumour through the development of more effective and less toxic treatments.

We unite a critical mass of multi-disciplinary personnel, infrastructure, and global collaborations across a four-stage pipeline: Pipeline-Stage 1 advances understanding of tumour biology and generates new disease models; Pipeline-Stage 2 deploys this knowledge to discover and validate new treatment targets; Pipeline-Stage 3 applies chemical biology to develop new probes and potential therapies; Pipeline-Stage 4 tests these and other promising treatments in preclinical trials.

During the prior funding period this pipeline: identified, developed and translated novel targets and treatments into clinical trials for children with cancer; established five new research groups; trained PhD and Master’s students; led/established numerous international consortia and meetings; and disseminated new tools, models and resources across the world.

During the next funding cycle, we will continue to conduct transformative research through our pipeline; but we are uniquely positioned to drive forward three leading-edge strategic themes addressing key unmet needs that are not currently being pursued by other investments in childhood brain tumour research.

Theme 1 will deploy the power of Artificial Intelligence/Machine Learning (AI/ML) through a new ‘Data-driven Virtual Brain Tumour Modelling’ pan-pipeline initiative to better understand and treat childhood brain tumours.

To achieve this, we have established major new partnerships with world-leaders in AI/ML at the Turing Institute and MD Anderson Cancer Centre (MDACC) as well as the rich AI/ML research environment at the University of Cambridge. We will also recruit a new research group dedicated to childhood brain tumour AI/ML research.

Together, we will leverage extensive multi-mode data of normal and malignant brain already generated by CRUK-CBTCE members to create the world’s first digital twin models of the hardest to treat childhood brain tumours (ZFTA-RELA ependymoma, MYC-driven neural tumours, high-grade glioma).

These models will be used in deep-learning experiments to better identify and prioritise new targets, conduct virtual clinical trials that predict efficacy and drug resistance, and understand drug-target interactions.

Theme 2 will engage the CRUK-CBTCE’s chemical biology team to characterise targets prioritised during the prior funding cycle, and explore new ones, to generate probes and prototype therapies e.g., small molecule degraders of ZFTA-RELA and ligandable pockets and/or degron motifs of transcription factors.

We will work closely with CRUK-CBTCE co-Investigators and collaborators who lead other major childhood brain tumour initiatives e.g., CRUK-PROTECT-Cancer Grand Challenge and CRUK-RadNet, to ensure our collective research is coordinated and shared; thereby achieving the greatest impact for patients.

Theme 3 includes our second new pan-pipeline initiative in ‘Early Brain Tumour Detection, Diagnosis and Monitoring’.

Led by our new CRUK-CBTCE principal site at the CRUK-Manchester Centre and with CRUK-Alliance for Cancer Early Detection, we will launch the UK’s first initiative aimed at detecting childhood brain tumours early and monitoring treatment.

Although cancer prevention and early cancer detection are major strategic objectives of CRUK, almost no research activities in this space exist in childhood cancer.

Hamerlik and her team at CRUK-Manchester will focus initially on their remarkable discovery that brain tumours can be readily and reproducibly detected in mice by mass spectrometry of the tear fluid proteome.

By pursuing these research Themes through our translational pipeline, we will thereby achieve CRUKs objectives to discover, detect, prevent, and treat, as well as further increase capacity in UK childhood brain tumour research.

Finally, we will extend our considerable efforts in training, networking and engagement by establishing the UK’s first childhood brain tumour PhD training Programme and continuing to lead our International Summer School and disease-group meeting series.

Our leadership of major national brain tumour initiatives e.g., the Tessa Jowell Brain Cancer Mission (TJBCM) and its Centres of Excellence for Children Programme, with whom we will share a national PPIE strategy, will ensure that our infrastructure, shared goals, and research impact the field of childhood brain tumour research and bring benefit to patients–spanning from early detection and fundamental research, through to novel treatments, biomarkers and monitoring strategies.