Circulating tumour DNA — looking beyond the blood

Abstract

Over the past decade, various liquid biopsy techniques have emerged as viable alternatives to the analysis of traditional tissue biopsy samples. Such surrogate ‘biopsies’ offer numerous advantages, including the relative ease of obtaining serial samples and overcoming the issues of interpreting one or more small tissue samples that might not reflect the entire tumour burden. To date, the majority of research in the area of liquid biopsies has focused on blood-based biomarkers, predominantly using plasma-derived circulating tumour DNA (ctDNA). However, ctDNA can also be obtained from various non-blood sources and these might offer unique advantages over plasma ctDNA. In this Review, we discuss advances in the analysis of ctDNA from non-blood sources, focusing on urine, cerebrospinal fluid, and pleural or peritoneal fluid, but also consider other sources of ctDNA. We discuss how these alternative sources can have a distinct yet complementary role to that of blood ctDNA analysis and consider various technical aspects of non-blood ctDNA assay development. We also reflect on the settings in which non-blood ctDNA can offer distinct advantages over plasma ctDNA and explore some of the challenges associated with translating these alternative assays from academia into clinical use.

C. elegans as a Powerful Tool for Cancer Screening

“…Non-invasive cancer detection using body fluids such as urine to detect volatile biomarkers is an exciting alternative and is less invasive than blood samples [ 25 ]. Interestingly, urine may also become a valid alternative to using blood for detecting and analyzing ctDNA [ 26 ]. Rapid developments have been observed in recent years in exploiting molecular biomarkers in urine to develop cancer screening and diagnostic tests, from using analytical techniques to exploiting living organisms such as nematodes or even ants [ 25 , 27 , 28 , 29 ].…”

“…Notably, patterns of volatiles organic compounds (VOCs) are produced by cancer cells and found in urine. A growing number of studies are linking different cancers to either an increase or decrease in levels of VOCs [ 18 , 21 , 26 , 31 , 32 , 33 ]. It is associated with the cancer smell, the end-product of metabolic changes producing patterns of volatile organic compounds (VOCs) observed in cancers [ 34 , 35 , 36 ].…”

The Role of Cell-Free DNA in Cancer Treatment Decision Making

“…It is not our goal to give detailed technical information concerning preparation of cf/ctDNA, but instead we want to improve the understanding of the clinical oncologists who are not experts in molecular biology, genetics, and next-generation sequencing (NGS). Regarding the technological advances in the methodology including analytical aspects and research areas, we refer to recent comprehensive reviews [ 10 , 11 , 12 , 13 , 14 , 15 , 16 ].…”

Three-dimensional ready-to-pick reservoir-based preconcentrator with a pillar-structured channel for miRNA applications

“…Many biomarkers regarding health status exist in the body fluids, including nucleic acids, proteins, enzymes, antibodies, vesicles, and cells (Bertrand et al, 2014;O'Connor et al, 2017;Hindson et al, 2013). In diagnostics, these biomarkers are used for early detection, disease prognosis, and therapeutic development (Tivey et al, 2022;Heitzer et al, 2019;Heikenfeld et al, 2019;Wang et al, 2016) (Wang et al, 2016;Heikenfeld et al, 2019;Heitzer et al, 2019;Tivey et al, 2022). For example, different types of microRNAs (miRNAs) contained in human blood or exosomes are promising cancer biomarkers, and certain groups of miRNAs are strongly related to the expression of specific cancer (Heikenfeld et al, 2019;Wang et al, 2016;Sajid et al, 2016;Purwidyantri et al, 2021) (Sajid et al, 2016;Wang et al, 2016;Heikenfeld et al, 2019;Purwidyantri et al, 2021).…”