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

• Published in: Cancer cell Vol. 42; no. 7; pp. 1301 - 1312.e7
• Main Authors: Casanova-Salas, Irene, Aguilar, Daniel, Cordoba-Terreros, Sarai, Agundez, Laura, Brandariz, Julian, Herranz, Nicolas, Mas, Alba, Gonzalez, Macarena, Morales-Barrera, Rafael, Sierra, Alexandre, Soriano-Navarro, Mario, Cresta, Pablo, Mir, Gisela, Simonetti, Sara, Rodrigues, Gonçalo, Arce-Gallego, Sara, Delgado-Serrano, Luisa, Agustí, Irene, Castellano-Sanz, Elena, Mast, Richard, de Albert, Matias, Celma, Ana, Santamaria, Anna, Gonzalez, Lucila, Castro, Natalia, Suanes, Maria del Mar, Hernández-Losa, Javier, Nonell, Lara, Peinado, Hector, Carles, Joan, Mateo, Joaquin
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 08.07.2024
• Subjects: Animals; biomarkers; Biomarkers, Tumor - blood; Biomarkers, Tumor - genetics; Cell Line, Tumor; Circulating Tumor DNA - blood; Circulating Tumor DNA - genetics; extracellular vesicles; Extracellular Vesicles - genetics; Extracellular Vesicles - metabolism; Gene Expression Profiling - methods; Gene Expression Regulation, Neoplastic; Genomics - methods; Humans; liquid biopsy; Liquid Biopsy - methods; Male; Mice; Neoplasm Metastasis; prostate cancer; Prostatic Neoplasms - blood; Prostatic Neoplasms - genetics; Prostatic Neoplasms - pathology; Transcriptome; transcriptomics; transcriptomics; prostate cancer; extracellular vesicles; biomarkers; liquid biopsy
• ISSN: 1535-6108; 1878-3686; 1878-3686
• DOI: 10.1016/j.ccell.2024.06.003

Extracellular vesicles (EVs) secreted by tumors are abundant in plasma, but their potential for interrogating the molecular features of tumors through multi-omic profiling remains widely unexplored. Genomic and transcriptomic profiling of circulating EV-DNA and EV-RNA isolated from in vitro and in vivo models of metastatic prostate cancer (mPC) reveal a high contribution of tumor material to EV-loaded DNA/RNA, validating the findings in two cohorts of longitudinal plasma samples collected from patients during androgen receptor signaling inhibitor (ARSI) or taxane-based therapy. EV-DNA genomic features recapitulate matched-patient biopsies and circulating tumor DNA (ctDNA) and associate with clinical progression. We develop a novel approach to enable transcriptomic profiling of EV-RNA (RExCuE). We report how the transcriptome of circulating EVs is enriched for tumor-associated transcripts, captures certain patient and tumor features, and reflects on-therapy tumor adaptation changes. Altogether, we show that EV profiling enables longitudinal transcriptomic and genomic profiling of mPC in liquid biopsy. [Display omitted] •EV profiling enables longitudinal interrogation of metastatic PC using liquid biopsy•EV-DNA genomic profiling recapitulates tumor features and associates with progression•RExCuE allows mRNA analysis in circulating EVs for liquid biopsies transcriptomic profiling•EV-RNA indicates early tumor adaptation changes during therapy in a non-invasive manner Casanova-Salas et al. uncover profiling of DNA and RNA isolated from circulating extracellular vesicles in blood samples from metastatic prostate cancer (mPC) patients. They present a method for detecting and monitoring tumor features and detecting emerging drug resistance drivers using liquid biopsies, facilitating precision treatments for prostate cancer.