Circulating tumor extracellular vesicles to monitor metastatic prostate cancer genomic and transcriptomic evolution. Circulating tumor extracellular vesicles to monitor metastatic prostate cancer genomic and transcriptomic evolution

Extracellular vesicles (EVs) secreted by tumors are abundant in plasma, but their potential for multi-omic profiling remains widely unexplored. Here, we pursued next-generation sequencing of circulating EV-DNA and EV-RNA in metastatic prostate cancer (mPC), using a range of in-vitro and in-vivo models, validating our findings in 35 mPC patients with longitudinal samples collected during androgen receptor signaling inhibitor (ARSI) therapy. EV-DNA copy-number (CN) profiles matched same-patient biopsies and ctDNA (p0.7, p<0.001). EV-RNAseq signatures at 4 weeks of therapy associated with clinical responses. Last, we derived a specific signature of ARSI response in EV-RNA in vivo that predicted response to therapy. In conclusion, EV profiling enables the study of mPC evolution at transcriptomics level in liquid biopsies. Overall design: Gene expression profiling analysis of RNA-seq data for C4-2 cells and matching EVs treated with Vehicle (VH) or Enzalutamide (EZ)