Treatment Resistance and Therapeutic Vulnerabilities in Metastatic Fusion-Positive Rhabdomyosarcoma

The National Pediatric Cancer Foundation (NPCF) aims to fund novel and innovative science and strives to make radical progress against pediatric cancers. Metastatic fusion positive rhabdomyosarcoma (MFPRMS) is an extremely rare sarcoma and presents with widely metastatic disease and an aggressive course. MFPRMS is often highly sensitive to therapy initially, with dramatic and even complete radiographic responses with treatment. However, disease almost inevitably recurs, with 3-year event-free survival rates of around 10%. There has been no recent improvement in survival outcomes for MFPRMS, and no promising new agents ready for testing in up-front clinical trials. The disease is highly challenging to study given its rarity, infrequent tissue acquisition, and predominance in children, a vulnerable population for research initiatives. 

Such dramatic responses followed consistently by recurrence begs the question: How does a cancer so sensitive to early treatment recur so readily; why are a population of cells intrinsically resistant or develop resistance to initial therapy which will help us identify and exploit vulnerabilities of resistant cells to reduce the relapse rate and improve outcome?