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. The aim is to speed up progress by prioritising promising options, allowing the research community and funders to drive future progress in a more streamlined way. In mid-2025, a workshop was hosted on desmoplastic small round cell tumours (DSRCT).

Before the workshop, participants received a detailed document explaining what is currently known about DSRCT, and a list of any known targets or treatments currently in development. Patient advocates set the scene at the workshop, by explaining their experience with current clinical practice and shared their views on the priorities and needs for improving treatments.

DSRCT is a very rare and aggressive cancer. It is a type of sarcoma and can occur anywhere in the body, but most commonly in the lining of the abdomen. It can develop at any age, though it is most common between the ages of 10 and 30. It is also more common in males. The tumours are formed of small round cells surrounded by a tough capsule made of connective tissue.

EWSR1-WT1 is a key cancer-driving gene found in everyone diagnosed with DSRCT.

At the workshop, the group selected molecules found in DSRCT that should be prioritised as potential targets for new drugs. These included:

1. EWSR1-WT1: This target is a very high priority. Blocking this target in laboratory tests has been shown to stop DSRCT cell growth. There is ongoing work to develop a novel treatment called TCR-T cell therapy, which modifies some of patient’s own immune cells (T cells), so that they can identify and destroy cancer cells by recognising molecules on the outside and inside of the cells. This type of treatment holds promise for targeting solid tumours. Drugs, known as degraders, which could break down EWSR1-WT1, may also be an interesting approach in the future.
2. LRRC15: levels of this molecule may be increased by EWSR1-WT1. LRRC15 sits on the surface of cancer cells making it an ideal target for drugs like antibodies, which can hunt down these kinds of molecules on cells. This also includes antibody-drug conjugates (ADCs) which can identify cancer cells and deliver drugs directly to them. LRRC15 was also identified as a priority target in the Paediatric Therapeutic Development Workshop on osteosarcoma.
3. SSTR3 and SSTR5: these molecules are usually involved in the control of certain hormones. SSTR3 and SSTR5 are very overactive in some DSRCT tumours. Targeting these could help slow or stop DSRCT growth, but the ideal method and type of drug is unclear. There is an ongoing clinical trial (PAMSARC) testing one approach to targeting these molecules.

In addition to prioritising the most promising targets for treatment, workshop participants also discussed treatments already being used in adult cancers, which also have the potential to treat DSRCT in children . These include medicines that target markers on cancer cells, e.g. HER2, B7H3, FGFR4 or Claudin-6. These could be targeted with antibody-drug conjugates and a trial evaluating an ADC for HER2, is producing some encouraging results. Existing medicines also exist to inhibit the action of another marker, NTRK3.

The group also discussed available drugs that can prevent cancer cells from fixing damage to their DNA, or block hormones that can fuel tumour growth (e.g. the androgen receptor, which most commonly responds to the hormone testosterone). The androgen receptor was previously included on the FDA’s Non-Relevant Molecular Target Leading to Waiver list – an official, regularly updated registry that identifies targets not considered relevant to the growth or progression of childhood cancers. This means that drugs previously developed against the androgen receptor did have not had to be tested in childhood cancers. Since our workshop took place, it has been removed from the list. Evaluating all of these ‘drug repurposing’ approaches in DSRCT is considered a very high priority, but obtaining the drugs for use in clinical trials in DSRCT, is a major barrier that still needs to be overcome.

Because DSRCT is so rare, participants also discussed how a global initiative in lab-based and clinical research is critical. A good example of this is the Foundation for the National Institute of Health (FNIH) ULTRA initiative, which aims to develop treatments for two ultra-rare cancer types, one of which is DSRCT. Outcomes from our workshops fed into a target and treatment selection meeting, which took place in January 2026. Work is now underway to support the development of treatments for DSRCT. Initiatives like this will ultimately help establish international clinical trials and collect data from more patients.

The outcomes of the Paediatric Therapeutic Development Workshop on DSRCT, can now be used by the research community and funders to help drive focused progress, together. The response to all the workshops has also shown how much the childhood cancer community values this approach. We 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.