Liquid biopsy: blood-based analyses of circulating cell-free DNA in xenografts

Abstract

The liquid biopsy concept has been introduced for circulating tumor cells more than 10 years ago (Pantel & Alix-Panabieres, 2010) and rapidly extended to cell-free DNA released from tumor cells (ctDNA; Lo et al, 2021) and other tumor-derived products such as circulating cell-free RNA (noncoding and messenger RNA), extracellular vesicles, or tumor-educated platelets (Alix-Panabières & Pantel, 2021). In this issue of EMBO Molecular Medicine, the report of Sauer et al (2022) demonstrates the feasibility of longitudinal monitoring of disease burden and response using ctDNA from dried blood spots in xenograft models.

Figure 1. Monitoring of ctDNA in cancer patients during tumor evolution

ctDNA analysis is based on the identification of tumor‐specific aberrations or epigenetic marks on circulating cell‐free DNA in blood plasma samples. It enables the development of new methods for early detection of primary cancer or disease relapse, monitoring the efficacy of cancer therapies, and determining therapeutic targets and resistance mechanisms to adapt therapy to the specific needs of an individual patient. The advantage is the noninvasive collection of tumor material and sequential monitoring of ctDNA in blood samples over time. However, blood volume is a critical factor in liquid biopsy analyses determining assay sensitivity. The size of the blood drops indicates the blood volumes required at different disease stages depending on the respective tumor burden in the cancer patient and the amount of ctDNA available in the blood sample.