Simple Summary
Outcomes for children and adolescents with rhabdomyosarcoma (RMS), the most common soft-tissue sarcoma of childhood, have not improved over the last four decades, despite discoveries from basic and translational studies of RMS. In this review, we synthesize recent insights into RMS biology, including emerging evidence for diverse cell of origin (s), advances in describing and modelling intra- and intertumoral heterogeneity, and mechanisms of cell-state plasticity. We discuss how the field can leverage these discoveries in combination with large-scale datasets and collaborative initiatives to potentially improve clinical outcomes for patients with RMS.
Abstract
Despite comprehensive and multi-modal therapy, outcomes for children and adolescents with rhabdomyosarcoma (RMS) have plateaued over the past four decades. This is not for a lack of progress in the basic and translational studies of RMS. Indeed, advances in animal models and in the acquisition and analysis of patient tissue samples have improved our understanding of RMS biology. Large-scale sequencing efforts have generated transcriptomic, genomic, and epigenomic datasets that highlight the heterogeneity of RMS and have the potential to improve prognostication and the application of precision medicine in patients with RMS. However, few of these discoveries have been clinically translated, and limitations to the accessibility, uniformity, and application of these new models and datasets hinder their utility. Here, we discuss how advances in understanding RMS biology, optimization of preclinical models, and strategies for translating basic science discoveries to the clinic can potentially improve outcomes for patients with RMS.