Paediatric therapeutic development workshop on desmoplastic small round cell tumours

The sixth Paediatric Therapeutic Development Workshop focused on desmoplastic small round cell tumours (DSRCT). Less than 20% of patients with DSRCT survive beyond 5 years and there is no targeted therapy for this disease, which represents an urgent unmet need for new therapeutics. High priority targets include the EWSR1::WT1 fusion protein, the oncogenic driver, and targeting a junction-derived neopeptide presented by HLA-A*03 and HLA-A*11 using a T-cell receptor (TCR) is a novel approach. Other targets (LRRC15, SSTR3 and SSTR5, NECTIN4, STEAP1 and mesothelin) require further validation. Targeting ERBB2/HER2 or claudin-6 by antibody-drug conjugates (ADCs) and NTRK3 by a small molecule inhibitor are promising approaches and are currently being evaluated. Existing clinical assets targeting (in order of importance) B7-H3, the DNA damage response, androgen signalling, FGFR4 and STEAP1 are also high priorities for evaluation in DSRCT, but obtaining therapeutics for clinical trials is a barrier. In view of the rarity of DSRCT, a global initiative in preclinical and clinical research to establish international trials and collect data from patients treated in a harmonised form would benefit patients. Progress can be made by a combined approach of developing new agents whilst evaluating existing therapeutics in well-designed trials.