Centre for Children and Young People's Cancer

Well-annotated data and AI-driven discovery

Childhood cancers are rare, resulting in few samples for analysis, small cohorts of patients in clinical trials, and fragmented datasets in the public domain. They also comprise a remarkable diversity of sub-types, providing challenges for translational biology, but also opportunities for improved molecular diagnostics.

We will build upon national initiatives (SMPaeds1/2), and individual retrospective and clinical trials cohorts to link with the Integrated Pathology Unit (IPU) and Data Science Team (DST) to generate and exploit multi-omic and single cell atlases of childhood cancer and their immune microenvironment (with the Centre for Translational Immunology, CTI), with high-quality clinical annotation, to better classify these tumours, map their developmental origins, and track their evolution under therapy.

Novel therapeutic approaches

Childhood cancers have their origins in development, whereby stalled maturation programmes result in cells locked in a progenitor-like state. They have bespoke drug targets which include developmentally-restricted transcription factors, and epigenetic modifiers which control cell plasticity, however these attract little pharma interest due to small patient populations, but also the limited availability of models and difficulty in running clinical trials.

We will link with the Centres for Target Validation (CTV) and Protein Degradation (CPD) to initiate specific drug discovery projects in this area (through the CBTCE where appropriate), and exploit the new Centre for In Vivo Modelling (CIVM) to assist in development of more physiologically relevant models of disease subtypes (including relapse/metastasis) to resource this.

Forward / reverse clinical translation

Via the NHSE WGS programme for all childhood cancer patients, and via SMPaeds2, we will increase the number of patients screened for biological molecular markers to guide entry into relevant clinical trials.

We will continue to develop more sophisticated and more efficient clinical trial designs such as platform/basket trials that require fewer patients to answer relevant trial questions, such as CONNECT-TarGeT and ITCC-ELICIT in PDHGG.

We will aim to learn from every patient on trial through implementation of co-clinical trials platforms using in vitro and in vivo patient avatars to inform biologically-rational treatment choices and resistance modelling.

We will incorporate minimally invasive translational laboratory and functional imaging biomarkers into early clinical trials wherever possible, to help understand disease response (or non-response) to new therapies, thus helping our iterative lifecycle style approach to paediatric cancer drug development.

Researchers at the ICR and The Royal Marsden hold key leadership roles in national and international clinical trials consortia (covering early and late phase studies), with direct evidence of translating laboratory discoveries to the clinic (e.g. Children’s Cancer and Leukaemia Group (CCLG), NIHR Clinical Study Groups, The Experimental Cancer Medicines Centre (ECMC) Network, International Society for Paediatric Oncology (SIOP) Europe including the SIOPE-Brain Tumour Group and SIOPEN (Neuroblastoma) Group, New Approaches to Neuroblastoma Therapy (NANT), European paediatric Soft tissue sarcoma Study Group (EpSSG), Collaborative Network for Neuro-oncology Clinical Trials (CONNECT), the UK Paediatric Transplant and Cell Therapy Network (‘ATICUS’) and the Innovative Therapies for Children with Cancer (ITCC) Consortium.

The ITCC comprises 62 clinical research centres and 25 academic research laboratories from across Europe (17 countries) with a focus on translating innovative laboratory discoveries to the clinic and developing novel therapies for the treatment of paediatric and adolescent cancers.

As part of an initially EU IMI-2 funded project, the ICR is a co-founder of a non-profit gGmbH spin-out company ITCC-P4 (ITCC Paediatric Preclinical Proof-of-Concept Platform), which offers preclinical testing on >400 childhood cancer models, many of which were developed by the ICR's researchers using samples from patients at The Royal Marsden. Faculty at the ICR are contracted entity experts of the gGmbH, providing an advisory role for experiment interpretation and ongoing strategy.

The ITCC-Brain Committee has also recently been awarded a €2M grant from Fight Kids Cancer to establish the Translational Accelerator Platform taking advantage of the ITCC-P4 offering, with the ICR forming the European PDHGG expert hub. 

• Dr Gabriela Kramer-Marek
• Professor Swen Hoelder
• Professor Chris Bakal
• Professor Trevor Graham
• Professor Alan Melcher
• Professor Simon Robinson