The Paediatric Therapeutic Development Workshops are a joint initiative between LifeArc, Innovative Therapies for Children and Adolescents with Cancer (ITCC), Cancer Research UK, Cancer Research Horizons and the Cancer Grand Challenges PROTECT team. The workshops bring together childhood cancer experts, including patient advocates, to help identify the most urgent needs and promising treatment ideas. Patient advocates set the scene for the workshops by explaining the patient experience within current clinical practice and sharing their views on priorities for improving treatments. The aim of the workshops is to speed up progress by prioritising promising options, allowing the research community and funders to help drive future progress in a more streamlined way. At the end of 2024, a workshop was hosted on medulloblastoma.

Medulloblastoma is the second most common brain tumour in children. It develops at the back of the brain and is likely to grow quickly. It can spread to other areas of the brain and spinal cord and around 30% of children have medulloblastoma that has already spread when they are first diagnosed.

There are low-risk and high-risk types of medulloblastoma. For children with the hardest-to-treat tumours, a key aim is to target the tumour’s ‘drivers’ (changes inside cancer cells that help them grow). However, there is a major shortage of new drugs for medulloblastoma. For low-risk medulloblastoma, the challenge is to reduce long-term side effects.

Before the workshop, participants received a detailed document explaining what we currently know about paediatric medulloblastoma and a list of drug targets and treatments currently in development.

The group selected several targets where there was no existing optimal drug, which they believe should be prioritised for potential new drug development. The selection was based on biology, preclinical investigations, and addressing a high unmet need within medulloblastoma. These included:

1. MYC and MYCN: the number of MYC and MYCN molecules is often much higher in medulloblastoma cells than normal cells. Some of the hardest-to-treat subtypes of medulloblastoma depend on MYC or MYCN activity to grow, making them important targets for drug development.
2. SRC: this target is permanently switched on in some types of medulloblastoma. Participants suggested that new types of medicines designed to remove SRC from the cell altogether (“degrader” drugs) might have potential.
3. OTX2: this molecule is involved in brain and sensory organ development and is produced at much higher levels in medulloblastoma cells than normal cells. It’s thought to play a role in all medulloblastoma subgroups, making it a promising target for all children with the disease.
4. GLI1/GLI2: these molecules pass on pro-cancer signals from other molecules, such as SRC. Medulloblastoma subtypes with poor survival often have extra copies of these genes.

The group also considered children with a type called WNT medulloblastoma – a subtype with very high cure rates. Here, the priority is to keep survival high, but to reduce the side effects of treatment. A unique characteristic of this type of medulloblastoma is that it disrupts the blood-brain barrier, which protects the brain and can make it hard for drugs to get into the brain. A “theranostic” antibody (a medicine that could help find and treat the tumour) may work well in this subtype because the ‘protection’ offered by the blood-brain barrier is weaker.

The workshop also highlighted molecules that could flag cancer cells to antibody-based treatments, allowing them to seek and tumours. Two promising targets in medulloblastoma are B7-H3 and GPC2, which could be used for treatments such as antibody–drug conjugates (antibodies that also deliver a cancer-killing drug to tumour cells).

The outcomes of this workshop can now be used by the research community and funders to help drive focused progress, together. The response to the workshop has also shown how much the community values this approach. We now believe there is appetite to build on this work moving forward, incorporating the innovative approaches and tools developed through these workshops. Investigators can apply for further support from projects like C-Further – a partnership between LifeArc, Cancer Research Horizons, and Great Ormond Street Hospital Charity – which focuses on developing new medicines specifically for children with cancer.

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