Abstract

Extracellular Vesicles as Novel Tools in Precision Medicine: Origins, Properties, and Molecular Cargo as Diagnostic and Prognostic Cancer Biomarkers

Andrew Godwin, Professor and Division Director, Genomic Diagnostics, Founding Director, Kansas Institute for Precision Medicine, Deputy Director, KU Cancer Center, University of Kansas Medical Center

Biomarkers are measurable biological indicators with numerous clinical applications each providing unique information about an individual's health status. The identification and development of new biomarkers is helping to advance the field of precision medicine. Biomarkers, including proteins, autoantibodies, RNA/DNA, metabolites, lipids, etc., continue to impact personalized health care, given each person’s disease has a unique pattern of biomarkers. In oncology, pathologic analysis of tumor tissue biopsies remains the gold standard for the initial diagnosis of cancer. However, liquid biopsies, which analyze tumor-derived material circulating in the bloodstream and other bodily fluids, are rapidly gaining traction in the clinic. These tests offer considerable potential in oncology, which include early detection, monitoring treatment response, and disease recurrence. Recently liquid biopsy-based biomarkers include circulating tumor cells, cell-free DNA/RNA, nanoparticles, and extracellular vesicles (EVs). Regarding the latter, EVs are showing great promise as circulating biomarkers. The International Society for Extracellular Vesicles define EVs as particles naturally released from the cell that are delimited by “a lipid bilayer and cannot replicate”. Center among EVs are nano-sized vesicles (40 to 150 nm) of endocytic origin also known as small EVs/exosomes, which are produced and released by most cell types under normal physiologic and in diseased states. sEVs carry cargo representative of their originating cell including nucleic acids, cytokines, membrane-bound receptors, and a wide assortment of other, biologically active lipids and proteins. Since sEVs/exosomes travel systemically throughout the body, efforts are underway to exploit them as potential biomarkers to detect and monitor disease states. Ways to isolate sEVs and characterize their cargo for cancer diagnostics and for monitoring early response to therapy will be discussed.