CtDNA release mechanisms in a therapeutic Ewing Sarcoma mouse model

EWSR1-FLI1 fusion sequence levels in circulating tumor DNA (ctDNA) have been shown to be a valuable biomarker in Ewing Sarcoma (EwS) patients, which can be used for prediction of treatment response and risk stratification. However, it remains unclear, under which circumstances ctDNA is released into the blood stream during tumor development and therapeutic intervention.

Different human EwS cell lines were injected intrafemorally in NSG mice. Tumors were treated locally by radiotherapy. Fusion sequences were quantified in mouse plasma throughout the whole experiment and tissue response was determined through histologic analysis, MRI, and PET-CT.

Quantified plasma levels were correlated to tumor activity, proliferation, mitosis, apoptosis and angiogenesis. Evaluation of plasma ctDNA levels, imaging data and histologic analysis revealed different responses of EwS tumors to radiotherapy.

A better understanding of ctDNA release contributes to the improved establishment of ctDNA as a non-invasive biomarker in EwS patients enabling therapy monitoring and risk stratification in clinical practice.

Publication History

Article published online:
17 May 2022