The National Pediatric Cancer Foundation has awarded a USD 1 million pediatric cancer research grant to JinSeok Park, PhD, at Children's Hospital Los Angeles, targeting metastatic fusion-positive rhabdomyosarcoma, an ultra-rare pediatric sarcoma driven by the PAX3-FOXO1 fusion oncoprotein. The award, announced May 1, 2026, follows a nationwide competitive proposal process and will support mechanistic and translational research aimed at understanding chemoresistance and recurrence in a disease where three-year event-free survival rates sit at approximately 10%.
MFPRMS is defined by the presence of the PAX3-FOXO1 chromosomal fusion, which produces an aberrant transcription factor that drives tumor growth. Although the disease typically shows sensitivity to initial chemotherapy — with responses that can be radiographically complete — relapse is near-universal, and no new agents have advanced to front-line clinical evaluation in recent years. The rarity of the disease, limited tissue availability, and the ethical and logistical complexity of conducting research in pediatric populations have historically constrained the pace of scientific progress.
Park's laboratory has identified a spatially organized cellular architecture within MFPRMS tumors that may help explain the pattern of treatment response followed by recurrence. At the invasive margins of tumor clusters, a population of cells expressing lower levels of PAX3-FOXO1 — designated leader cells — extends into surrounding tissue, creating physical space for tumor expansion. A second population, follower cells concentrated in the tumor core, expresses higher levels of PAX3-FOXO1 and proliferates at a faster rate, filling the space opened by leader cell invasion and sustaining outward tumor growth.
The mechanistic hypothesis Park's team will investigate is that the leader cell population, by virtue of its reduced PAX3-FOXO1 expression, proliferates more slowly and may therefore be less susceptible to cytotoxic agents that target rapidly dividing cells. Under this model, leader cells function as a chemoresistant shield, surviving treatment that eliminates the more proliferative follower cell core, and subsequently seeding recurrence. The funded research will examine how MFPRMS tumors regulate PAX3-FOXO1 expression at their margins and how that regulation connects to drug resistance at the cellular level.