Circulating tumor extracellular vesicles to monitor metastatic prostate cancer genomics and transcriptomic evolution
- PMID: 38981440
- DOI: 10.1016/j.ccell.2024.06.003
Circulating tumor extracellular vesicles to monitor metastatic prostate cancer genomics and transcriptomic evolution
Abstract
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.
Keywords: biomarkers; extracellular vesicles; liquid biopsy; prostate cancer; transcriptomics.
Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.
Conflict of interest statement
Declaration of interests R.M.-B.: consulting or advisory and/or speaker bureaus for Sanofi Aventis, AstraZeneca, Merck Sharp & Dohme, Astellas, BMS, and travel and accommodation expenses from Roche, Sanofi Aventis, Astellas, Janssen, Merck Sharp & Dohme, Bayer, and Pfizer. J.C. received consulting and speaker’s fees from Bayer, Johnson & Johnson, Bristol-Myers Squibb, Astellas Pharma, Pfizer, Sanofi, MSD Oncology, Roche, AstraZeneca and Asofarma, and research support from AB Science, Aragon Pharmaceuticals, Arog Pharmaceuticals INC, Astellas Pharma., Astrazeneca AB, Aveo Pharmaceuticals INC, Bayer AG, Blueprint Medicines Corporation, BN Immunotherapeutics INC, Boehringer Ingelheim, Bristol-Myers Squibb International Corporation (BMS), Clovis Oncology INC, Cougar Biotechnology INC, Deciphera Pharmaceuticals LLC, Exelixis INC, F. Hoffmann-La Roche LTD, Genentech INC, Glaxosmithkline, SA, Incyte Corporation, Janssen-Cilag International NV, Karyopharm Therapeutics INC, Laboratoires Leurquin Mediolanum SAS, Lilly SA, Medimmune, Millennium Pharmaceuticals INC., Nanobiotix SA, Novartis Farmacéutica SA, Pfizer, S.L.U, Puma Biotechnology INC, Sanofi-Aventis SA, SFJ Pharma LTD. II, Teva Pharma S.L.U. J.M. has served as advisor for AstraZeneca, Amunix/Sanofi, Daichii-Sankyo, Janssen, MSD; Pfizer and Roche; he is member of the scientific board for Nuage Therapeutics and is involved as investigator in several pharma-sponsored clinical trials, none of them related to this work. He is also the PI of grants funded by AstraZeneca, Amgen, and Pfizer to VHIO (institution), including grant NCR-19-20035, relevant to this work.
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