Extracellular Vesicles and Circulating Tumour Cells - complementary liquid biopsies or standalone concepts?

Abstract

Liquid biopsies do promise a lot, but are they keeping it? In the past decade, additional novel biomarkers qualified to be called like that, of which, some took necessary hurdles resulting in FDA approval and clinical use. Some others are since a while around, well known and were once regarded to be a game changer in cancer diagnosis or cancer screening. But, during their clinical use limitations were observed from statistical significance and questions raised regarding their robustness, that eventually led to be dropped from associated clinical guidelines for certain applications including cancer diagnosis. The purpose of this review isn't to give a broad overview of all current liquid biopsy as biomarkers, weight them and promise a brighter future in cancer prevention, but rather to take a deeper look on two of those who do qualify to be called liquid biopsies now or then. These two are probably of greatest interest conceptually and methodically, and likely have the highest chances to be in clinical use soon, with a portfolio extension over their original conceptual usage. We aim to dig deeper beyond cancer diagnosis or cancer screening. Actually, we aim to review in depth extracellular vesicles (EVs) and compare with circulating tumour cells (CTCs). The latter methodology is partially FDA approved and in clinical use. We will lay out similarities as taking advantage of surface antigens on EVs and CTCs in case of characterization and quantification. But drawing readers' attention to downstream application based on capture/isolation methodology and simply on their overall nature, here apparently being living material eventually recoverable as CTCs are vs. dead material with transient effects on recipient cell as in case of EVs. All this we try to bring in perspective, compare and conclude towards which future direction we are aiming for, or should aim for. Do we announce a winner between CTCs vs EVs? No, but we provide good reasons to intensify research on them.

Small Extracellular Vesicles and Their Involvement in Cancer Resistance: An Up-to-Date Review

“…Understanding these mechanisms and precisely following the axis of ncRNA-miR-mRNA is crucial for the future use of exosome inhibitors in cancer therapy. Based on the analyzed research and our observations [ 14 , 30 , 166 , 167 ], it must be noted that both small and large EVs are the future of personalized medicine, including not only in the diagnosis and prognosis of cancer patients but also as a treatment strategy. Such an application of our knowledge of exosomes can rely on two potential activities: (1) inhibiting the release of exosomes [ 168 ] and (2) using exosomes as a platform for chemotherapeutic agent transport [ 169 , 170 ] and as a ‘freighter’ for therapeutic RNAs and peptides [ 171 ].…”

“…This review describes the importance of EVs for regulating cancer cell responses to chemotherapy by focusing on the most up-to-date and clinically quintessential relationships between EVs and chemoresistance. As our team, a little while back, noted, most studies have identified the centrality of the role of exosomal ncRNAs in chemoresistance [ 30 ]. Hence, we present here the mechanisms by which these types of EVs modulate the response to cytotoxic drugs by microRNAs (miRNAs, miRs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), all of which have a cardinal role in the regulation of gene expression [ 31 , 32 , 33 ].…”

“…Reasoning from this fact, the studies presented in this review have shown that exosomes may likewise be involved in the sensitization of cancer cells to cytotoxic drugs. These opposite properties of exosomes, induction, or reduction of chemoresistance, are determined by their cargo during intercellular communication [ 30 ]. Moreover, exosomes not only modulate the response to cytotoxic therapy but can also induce radioresistance [ 34 ].…”

Exosome-based nanoimmunotherapy targeting TAMs, a promising strategy for glioma

“…Exosome-based liquid biopsies provide information about the actions of tumor cells and present possible applications for tumor diagnosis, therapeutic response monitoring, and prognosis evaluation [ 55 , 69 ]. Specifically, compared to circulating tumor cells, exosomes give better sensitivity during the initiating process, which is closely linked to carcinogenesis [ 70 ].…”

Effects of Exosomes on Tumor Bioregulation and Diagnosis

“…The antigen presentation of exosomes can also serve as a good vehicle for cancer vaccines, providing a new direction for cancer immunotherapy. With the continuous development of medical technology, the diagnostic efficacy of many classical tumor markers is no longer sufficient, 49 and scholars have been searching for biomarkers with higher specificity and sensitivity. Exosomes can be found in blood, urine, cerebrospinal fluid, and even saliva, making it easier to obtain samples for testing.…”