Purpose of Review
Ewing sarcoma is the second most common bone cancer seen in children and adolescents. Previous reports have demonstrated that the main driver of malignancy in this disease is an aberrant transcription factor that is expressed by gene fusions between the EWSR1 gene and an ETS family transcription factor such as FLI1 or ERG. Here we review recent preclinical and clinical advances in drug development for the treatment of Ewing sarcoma. We also discuss the rationale for promising combination therapies that have been considered in the interest of developing treatments for Ewing sarcoma.
Recent Findings
The main driver of malignancy in this disease is EWS-FLI1. There have been valiant efforts to develop targeted therapies targeting EWS-FLI1, epigenetic factors, factors that affect transcription and the repurposing of previously approved drugs has also been of interest.
Summary
The underlying mechanisms of how EWS-FLI1 contributes to malignancy in Ewing sarcoma have been extensively studied. Through these observations, EWS-FLI1 targeting and inhibition of aberrant transcription of downstream targets has been proposed as a potential pharmacologic treatment. Improved understanding of how newly developed compounds affect this disease, keeping associated toxicities in mind have led to structure activity relationship studies that have demonstrated improved efficacy and toxicity when treating at the preclinical level. Although there have been many challenges translating these promising results in the clinic, there are further studies ongoing to improve these efforts.