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Liquid biopsy analysis in cancer diagnostics. Andersson D, Kubista M, Ståhlberg A. Mol Aspects Med. 2020 Apr;72:100839. doi: 10.1016/j.mam.2019.100839.
In this issue, molecular aspects of liquid biopsy analysis in cancer diagnostics are reviewed and discussed. So far, liquid biopsy analysis has been concentrated on a single analyte, most often circulating tumor cells (CTCs) or circulating tumor DNA (ctDNA) (Keller and Pantel, 2019), but other analytes are available for study, including mRNA, miRNA, lncRNA, extracellular vesicles, proteins, metabolites, and tumor-educated platelets. Liquid biopsy analysis includes several ex- perimental steps and Geeurickx and Hendrix outline the importance of pre-analytical procedures and the need for standardization for re- producible analysis. The existence of CTCs has been known since 1869, but it was first in the late 90s that their clinical potential was re- cognized (Siravegna et al., 2017). Cortés-Hernández et al. review stra- tegies for the functional assessment of CTCs to elucidate their meta- static competence. Werner et al. focus on the role of keratins as markers for CTCs and their biological properties and relevance in cancer me- tastasis. Although the first report on circulating cell-free DNA was published already in the late 40s, it was not until four decades later that the presence of ctDNA was reported in plasma of cancer patients (Mandel and Metais, 1948; Stroun et al., 1989). CtDNA is released from cells undergoing apoptosis, necrosis and through active secretion, and it is typically cleared from the bloodstream within hours by nuclease activity, by the liver and spleen, and excretion via the kidneys (Bronkhorst et al., 2019). Andersson et al. review the current challenges and use of ctDNA analysis in pediatric cancers. Namløs et al. discuss the potential of ctDNA as biomarker in sarcomas, while Gasi Tandefelt and de Bono focus on the clinical implications of prostate cancer genomics and how ctDNA may facilitate treatment management. In addition to CTCs and ctDNA, different types of RNA molecules, in particular miRNA, are gaining interest as cancer biomarkers in liquid biopsies. Gines et al. summarize the most promising techniques to analyze miRNA, focusing on isothermal approaches. Valihrach et al. highlight important aspects of the experimental workflow for miRNA analysis in liquid biopsies, while Lampignano et al. focus on the clinical aspects of miRNA analysis in lung cancer. Alongside prostate-specific antigen, other proteins, such as CA125, CEA, CA19-9, and S100, are clinically used blood biomarkers in cancer, but many have limited specificity. Gidwani et al. discuss protein glycosylation and how it can be analyzed as well as applied as a biomarker in liquid biopsies.
Number of publications per year with the search term ‘“liquid biopsy” OR “liquid biopsies” AND “cancer”’ at PubMed, 19 December 2019.