# Biological Advances and Current Challenges for Pediatric Rhabdomyosarcoma

## TL;DR

This review discusses recent biological insights into pediatric rhabdomyosarcoma and how they might lead to better treatments, despite limited clinical progress.

## Contribution

The paper synthesizes recent biological discoveries and proposes strategies to translate these into improved clinical outcomes for RMS patients.

## Key findings

- Recent studies suggest diverse cell origins and mechanisms of heterogeneity in RMS.
- Large-scale datasets have improved understanding of RMS biology but face clinical translation barriers.
- Optimization of preclinical models and collaborative initiatives could enhance RMS treatment outcomes.

## Abstract

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 made in basic and translational studies of RMS. In this review, we synthesize recent insights into RMS biology including emerging evidence for the possibility of diverse cell(s) of origin, advances in describing and modelling intra- and intertumoral heterogeneity, and emerging 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.

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/or patient tissue sample acquisition and analysis 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.