The Paediatric Therapeutic Development Workshops are a joint initiative between LifeArc, Innovative Therapies for Children and Adolescents with Cancer (ITCC), Cancer Research UK and Cancer Research Horizons. The workshops bring together childhood cancer experts to help identify the most urgent needs and promising treatment ideas. The aim is to speed up progress by prioritising promising options, allowing the research community and funders to help drive future treatments in a more streamlined way. Patient advocates opened the workshop by sharing first-hand insight into the treatment and clinical experience of rhabdomyosarcoma, helping to identify priorities for improvement.

At the end of 2024, a workshop was hosted on rhabdomyosarcoma – a type of soft tissue sarcoma. There is a major shortage of new drugs for rhabdomyosarcoma. The workshop focused on the main subtypes affecting children:

• Alveolar rhabdomyosarcoma (occurs mainly in older children and teenagers)
• Embryonal rhabdomyosarcoma (occurs mainly in young children)

Participants received a detailed document explaining what is currently known about rhabdomyosarcoma, along with a list of drug targets and treatments in development.

The group selected several targets involved in the development of rhabdomyosarcoma where no effective treatment currently exists and recommended these be prioritised for future drug development. The selection was based on biology, preclinical investigations and addressing a high unmet need within rhabdomyosarcoma. These included:

1. AX3-FOXO1 and PAX7-FOXO1 fusion genes: Approximately 20% of rhabdomyosarcoma tumours are caused when a gene called FOXO1 fuses together with the PAX3 gene or PAX7 gene. The resulting ‘fusion gene’ leads to the production of a faulty molecule that ‘switches on’ cancer-causing signals. The group suggested targeted protein degradation (a method which tags the faulty protein for destruction) as the best treatment approach.
2. FGFR4: This molecule is one of several activated by the faulty PAX-FOXO1 fusion gene. It’s also involved in rhabdomyosarcomas that aren’t caused by the fusion gene, making it an important drug target across disease subtypes. Using antibodies to deliver cancer-killing drugs directly to FGFR4 (known as antibody–drug conjugates) could be a promising approach.
3. MYOD1: This protein is involved in normal muscle development, but in rhabdomyosarcoma its function is altered, and it can no longer convert embryonic muscle cells into mature muscle tissue. Removing faulty MYOD1 by targeted protein degradation could be a promising treatment approach.
4. ROR2: This molecule helps to control normal cell growth and movement during muscle development. It’s known to promote tumour growth and invasiveness in other cancers. It has also been identified as a high-priority target in a Paediatric Therapeutic Development Workshop on osteosarcoma. An antibody–drug conjugate may be the best approach for targeting ROR2.
5. P300 and CBP: This pair of molecules passes on pro-cancer signals from PAX-FOXO1 and also controls activation of MYOD1 in muscle development.

In addition to these targets, MYCN, a known driver of many cancers, is a high-priority in fusion-positive rhabdomyosarcoma. However, there are substantial challenges of targeting MYCN directly, and both indirect and direct approaches should be pursued.

The workshop also examined how to harness the power of the immune system against rhabdomyosarcoma. The discussion highlighted targets that could be used to help antibody-based treatments reach and destroy tumour cells. Antibody–drug conjugates are in development against the target B7‑H3 and, if promising, should be explored in clinical trials for rhabdomyosarcoma.

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.