Abstract
In recent years, the rapid development of next-generation sequencing (NGS) has led to a significant increase in accuracy toward molecular profiling, allowing noninvasive and real-time detection of novel biomarkers for cancer screening and dynamic monitoring of disease development. Currently, the biggest challenge liquid biopsies face is the selection of the highest signal-bearing tissues (blood/urine or others) and components for diagnosis, being either circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), or extracellular vesicles (EVs). This chapter describes the process of identifying cancer-associated molecular signals from liquid biopsies. First, we address strategies in selecting and processing samples for sequencing, and technical considerations involved in liquid biopsies under three settings: early detection, cancer diagnosis, and metastatic monitoring. Next, we discuss the methods and challenges to identify and validate prognostic signals, such as tumor burden or stage from CTC, targeted and nontargeted mutations from ctDNA, or noncoding RNAs from EVs. Finally, we review the current landscape of novel biomarkers and ongoing clinical trials for liquid biopsies to discuss the potential avenues for future precision medicine and clinical implementation.
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