Abstract

Longitudinal Analysis of Serum-derived Exosomal RNA Identifies Biomarkers of Treatment Response to Targeted Therapy for Glioblastoma

Leonora Balaj, Instructor, Mass General Hospital (MGH)/Harvard Medical School

We performed longitudinal whole-transcriptome profiling of serum exosomes from patients suffering recurrent glioblastoma (GBM) enrolled in a clinical trial to assess response to Dacomitinib, a second-generation irreversible EGFR tyrosine kinase inhibitor. All patients underwent daily oral administration of Dacomitinib and blood samples were collected immediately prior to first treatment and monthly thereafter. Deep sequencing of exosomal RNA (exRNA), derived from just 2ml of patient serum, revealed robust signatures of treatment response, as defined by 6-month progression-free survival. Furthemore, in comparison to healthy control serum we find hundreds of transcripts exhibiting differential abundance in pre-treatment GBM patients that may serve as general non-invasive biomarkers for this devastating disease. This study represents the first longitudinal profiling of the exosomal transcriptome and these findings are a tantalizing step toward exosome-based biomarkers for the detection of GBM and for patient stratification and monitoring.