Liquid biopsy: Potential and challenges

Current molecular diagnostics in cancer patients is based on needle biopsies, which, however, face serious limitations which can lead to false decisions. Individual tumors consist of diverse subpopulations, and the small amount of tissue obtained by needle biopsies may not represent the most aggressive subclones. Moreover, some tumor entities such as lung cancer are located at remote sites and a needle biopsy can be very difficult and at high risk. Finally, the mere analysis of the resected primary tumor alone (current standard practise in oncology) may provide misleading information with regard to the characteristics of metastases, the key target for systemic anticancer therapy. Distant metastases can harbor unique genomic characteristics not detectable in the corresponding primary tumor of the same patient and metastases located at different sites show a considerable intra-patient heterogeneity (Gerlinger et al., 2013). Thus, even if re-evaluation of tumor characteristics based on the biopsy of the most accessible metastasis is possible, it may not reveal sufficient information for treatment decisions. This dilemma has led to a new diagnostic concept: the Liquid Biopsy, i.e., analysis of circulating tumor cells (CTCs) and cell-free circulating nucleic acids (in particular circulating tumor DNA -ctDNA) released into the peripheral blood from the primary tumor and/or metastatic deposits. In this special issue, we discuss the current challenges and future perspectives of CTCs and ctDNA as biomarkers in clinical oncology. Both CTCs and ctDNA are interesting complementary biomarkers that can be used in future trials assessing new drugs or drug combinations. Sensitivemethods have been developed to capture CTCs in the peripheral blood and disseminated tumor cells (DTCs) in the bone marrow at the single cell level in cancer patients (Alix-Panabi eres and Pantel, 2014). The analysis of CTCs may provide clinically relevant information as “liquid biopsy” (Heitzer et al., 2013; Pantel and Alix-Panabi eres, 2013; Pantel et al., 2013; Schwarzenbach et al., 2014). Moreover, analysis of DTCs provide new insights into the process of “cancer dormancy” (LeBleu et al., 2014; Lu et al., 2011; Uhr and Pantel, 2011) and also lead to the discovery of new molecules