Liquid Biopsies in Cancer Diagnosis, Monitoring, and Prognosis

Abstract

Liquid biopsy, consisting in the non-invasive analysis of circulating tumor-derived material (the Tumor Circulome), represents an innovative tool in precision oncology to overcome current limitations associated with tissue biopsies. Within the tumor circulome, ctDNA and CTCs are the only components whose clinical application is FDA-cleared. Extracellular vesicles, ctRNA and tumor-educated platelets are relatively novel tumor circulome constituents with promising potential at each stage of cancer management. Here, we discuss the clinical applications of each element of the tumor circulome and the prevailing factors that currently limit implementation in clinical practice. We also detail the most recent technological developments in the field, which demonstrate potential in improving the clinical value of liquid biopsies. Commented [GDR3R2]: Thanks for doing that Commented [MK(2]: Please include all weblinks in a separate section before "References", entitled "Resources" Commented [MK(1]: Please include all weblinks in a separate section before "References", entitled "Resources" Commented [MK(4]: Since this is how it is depicted in the Figure. Commented [MK(5]: I suggest that this be converted into "Key Figure". The Figure represents the contents of the review well. Commented [MK(6]: Are the authors talking about advances in sample isolation? I'd encourage you to give examples to align the readers to what advancements the authors are referring to. Commented [GDR7R6]: Done with some of the innovations discussed in the following chapters.

Metabolite therapy guided by liquid biopsy proteomics delays retinal neurodegeneration

“…This advancement is exemplified in the personalized treatment of cancer, where circulating tumor-derived material (e.g. circulating tumor DNA/RNA, extracellular vesicles, and cells) are detected in the blood [59,60]. These cellular biomarkers of the tumor microenvironment aid clinicians to better determine the appropriate therapeutic approach and predict prognosis.…”

Ca2+ mediates extracellular vesicle biogenesis through alternate pathways in malignancy

“…The significance of EVs is not restricted to cellular signalling and they have emerged as novel drug-delivery vehicles, and important biomarkers [10,11].…”

Current progress in the clinical use of circulating tumor cells as prognostic biomarkers

“…These include circulating tumor DNA (cell-free DNA), circulating tumor proteins, tumor-derived extracellular vesicles, tumor-educated platelets, and circulating tumor RNA, including microRNA. 109 All these biomarkers ideally should be used together with CTCs to provide a comprehensive picture of a cancer via its "tumor circulome," a complete profile of the circulating biological components derived from tumor tissue. Together with the other "tumor circulome" biomarkers, CTCs appear to hold great promise for precision prognosis and personalized cancer treatment.…”

“…CTCs are not the only component of liquid biopsies; the same blood samples that provide CTCs also contain several other biomarkers for cancer prognosis. These include circulating tumor DNA (cell‐free DNA), circulating tumor proteins, tumor‐derived extracellular vesicles, tumor‐educated platelets, and circulating tumor RNA, including microRNA . All these biomarkers ideally should be used together with CTCs to provide a comprehensive picture of a cancer via its “tumor circulome,” a complete profile of the circulating biological components derived from tumor tissue.…”