Translational aspects of Desmoplastic small round cell tumor (DSRCT): An expert consensus paper from the OCTOPUS...

Desmoplastic Small Round Cell Tumor (DSRCT) is an ultra-rare, highly aggressive sarcoma that predominantly affects young individuals. DSRCT is defined by the characteristic chromosomal translocation t(11;22) (p13;q12), which results in the oncogenic EWSR1::WT1 fusion gene. DSRCT typically presents as multiple, disseminated nodules within the abdominopelvic cavity. Patients with DSRCT typically receive an intensive multimodal treatment regimen comprising multi-agent chemotherapy, extensive cytoreductive surgery, that could be followed by whole abdominopelvic radiotherapy. Attempts to improve patient outcomes over the past two decades have yielded limited results, leading to a persistent lack of improvement in prognosis. There is an urgent, unmet clinical need for innovative and effective treatments guided by a deeper understanding of DSRCT biology. Recent efforts have successfully generated extensive multi-omic data and a growing number of patient-derived models. This information has deepened our understanding of the EWSR1::WT1 translocation's oncogenic mechanisms and revealed critical DSRCT dependencies, leading to the identification of several putative therapeutic targets. Clinical translation of these findings as well as conduction of further preclinical research requires an international, multidisciplinary collaborative effort to propel preclinical and clinical studies. This review was conducted by the DSRCT Working Group of OCTOPUS ("Optimising Combination Therapy fOr Paediatric, adolescent and yoUng adult patients with non-rhabdomyosarcoma soft tissue Sarcomas") to consolidate existing knowledge on preclinical translational aspects of DSRCT and guide future cooperative research.