Circulating Exosome Cargoes Contain Functionally Diverse Cancer Biomarkers: From Biogenesis and Function to Purification and Potential Translational Utility

Abstract

Although diagnostic and therapeutic treatments of cancer have tremendously improved over the past two decades, the indolent nature of its symptoms has made early detection challenging. Thus, inter-disciplinary (genomic, transcriptomic, proteomic, and lipidomic) research efforts have been focused on the non-invasive identification of unique “silver bullet” cancer biomarkers for the design of ultra-sensitive molecular diagnostic assays. Circulating tumor biomarkers, such as CTCs and ctDNAs, which are released by tumors in the circulation, have already demonstrated their clinical utility for the non-invasive detection of certain solid tumors. Considering that exosomes are actively produced by all cells, including tumor cells, and can be found in the circulation, they have been extensively assessed for their potential as a source of circulating cell-specific biomarkers. Exosomes are particularly appealing because they represent a stable and encapsulated reservoir of active biological compounds that may be useful for the non-invasive detection of cancer. T biogenesis of these extracellular vesicles is profoundly altered during carcinogenesis, but because they harbor unique or uniquely combined surface proteins, cancer biomarker studies have been focused on their purification from biofluids, for the analysis of their RNA, DNA, protein, and lipid cargoes. In this review, we evaluate the biogenesis of normal and cancer exosomes, provide extensive information on the state of the art, the current purification methods, and the technologies employed for genomic, transcriptomic, proteomic, and lipidomic evaluation of their cargoes. Our thorough examination of the literature highlights the current limitations and promising future of exosomes as a liquid biopsy for the identification of circulating tumor biomarkers.

Dynamic Interplay in Tumor Ecosystems: Communication between Hepatoma Cells and Fibroblasts

“…The secretion of EVs is a regular activity in both normal and compromised cells. EVs are either released by exocytosis of multivesicular bodies or by plasma membrane shedding [ 29 ]. Their size and content may vary depending on the originating cell and they can be harnessed for diverse applications such as drug delivery, biomarker identification, early detection of tumors, cancer diagnosis, and disease management [ 29 , 30 , 31 ].…”

Exosomes: a promising avenue for cancer diagnosis beyond treatment

“…Furthermore, the molecular cargo of exosomes can be meticulously analyzed to identify specific cancer types and discern their unique characteristics ( Mitchell et al, 2022 ). This valuable information provides a foundation for the development of personalized treatment plans tailored to the patient’s specific cancer subtype ( Srivastava et al, 2018 ).…”

Smart Lipid‐Based Nanoparticles in Lung Cancer Treatment: Current Status and Future Directions

“…[180,181] EVs were first discovered in the 1980s and were believed to be a means of cellular waste disposal; however, in 2012, their primary function as a signaling mechanism enabling cells to connect with other cells throughout the body was uncovered. [182] Exosomes are released by all cells in the body, and each one carries its own special payload or surface ligand to accomplish a specialized biological task. [183,184] However, cancer cells are distinct in that they release tenfold more exosomes than healthy cells, and these exosomes contain a wide variety of aberrant DNAs, RNAs, proteins, and other chemicals that can contribute to transforming healthy cells into malignant ones by affecting the TME, [185,186] thereby aiding in the growth and progression of cancer.…”