Handbook of Targeted Cancer Therapy and Immunotherapy

94 Introduction In this section we will discuss liquid biopsies, specifically pertaining to cell-free DNA (cfDNA) or circulating tumor DNA (ctDNA), and its applicability in the management of gastrointestinal (GI) cancer patients. Liquid biopsies are simple, noninvasive tests in biologic fluids such as blood or urine that enable the measurement of clinically relevant biomarkers. There are many analytes within the circulatory system that can serve as markers of disease states, such as proteins, messenger mRNA, micro RNA (miRNA), and cell-free DNA (cfDNA). cfDNA had been first reported in 1948 by Mandel and Metais in human plasma and consists of fragments of genetic material found outside of the cell (1). In 1977, Leon et al. (2) had reported elevated levels of cfDNA in cancer patients when compared to healthy individuals. cfDNA that has been released from tumor cells is referred to as ctDNA and can vary in range from a minute portion ( < 1%) of an individual’s total cfDNA to a relatively high abundance correlating with tumor burden. cfDNA or ctDNA can serve as a surrogate marker of disease in cancer patients, and three potential mechanisms for its release into circulation have been described: necrosis, apoptosis, and active secretion (Figure 10.1) (3). Over the past decades, with significant advancements in methods for ctDNA detection, its applicability in the clinical care of cancer patients has been garnering significant interest and re search. This includes its use as prognostic and/or predictive markers, in the detection of disease recurrence after definitive therapy, in the management of minimal residual disease (MRD), in mon itoring response to therapy, and in identification of resistance mechanisms after exposure to tar geted therapies (Figure 10.1). Through sampling of the blood for ctDNA at multiple time points during a patient’s cancer treatment, liquid biopsies can aid in the longitudinal evaluation of a pa tient’s cancer genome. In the sections below, we detail clinical applications of ctDNA within the context of common GI malignancies.

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