Functional studies on circulating and disseminated tumor cells in carcinoma patients

Abstract

Despite numerous clinical studies indicating the clinical relevance of circulating tumor cells (CTCs) in blood and disseminated tumor cells (DTCs) in the bone marrow of cancer patients, the functional properties of these cells are largely unknown. The focus of this review is to emphasize how functional studies on viable CTCs and DTCs can enlarge the spectrum of applications of "liquid biopsies". The low number of CTCs in the peripheral blood and DTCs in the bone marrow and the fact that carcinoma cells are difficult to culture are major challenges. Significant advances in the in vitro and in vivo expansion of CTCs and DTCs from cancer patients have been achieved, which enable us now to study the functional properties of these cells. Here, we discuss published data about functional studies on CTCs and DTCs using in vitro cultivation and in vivo xenograft models. Functional analyses on CTCs and DTCs offer the possibility to identify the metastasis-initiating cells. Moreover, CTC-derived cell lines and xenografts might point to new therapeutic targets and can be used for drug development.

Keywords: Biomarkers; CTCs; Cell lines; DTCs; Liquid biopsy; Solid tumors.

Figure 1

Functional studies with CTCs and DTCs using in vitro and/or in vivo models for personalized clinical management of patients with solid cancers. A. CTCs and DTCs are first enriched from blood samples or bone marrow aspirates of cancer patients (i.e., lung, breast, prostate, colon cancer), respectively. CTCs or DTCs are subsequently expanded in special culture medium or in immunodeficient mice. The last step is getting CTC/DTC lines or xenografts, respectively. B. Viable CTCs can be enumerated using a functional assay (EPISPOT assay) leading to prognostic information. CTCs can be cultured in vitro and an in‐depth characterization of established CTC lines may identify metastasis‐initiator cells, a crucial point for new drug development. To potentially eradicate metastatic disease, CTCs can be expanded in vivo for therapy testing and better understanding of drug resistance mechanisms.