State of the Art in the Propagation of Circulating Tumor Cells

Circulating tumor cells (CTCs) are a group of cells that travel through the circulatory system of a cancer patient, sowing distant sites and forming the seeds for metastatic nodules. Given the unique role of CTCs, the study of this cell population could enable significant strides in understanding metastasis. The clinical importance of CTCs for predicting overall survival has been routinely demonstrated. Recently, advancements in culturing and expanding viable CTCs ex vivo made in the last two decades have further enabled researchers to properly interrogate this new frontier of metastatic research. Expansion of CTCs through in vitro cultures and in vivo CTC-derived xenograft models (CDXs) has resulted in groundbreaking findings significantly improving the rather simplistic models of metastasis previously used. In this chapter, we will focus on advancements made toward isolating and culturing CTCs both in a tissue culture plate and through the formation of CDX models. We will highlight two eras of CTC culture: one focused on growing viable epithelial cells and the other focused on modeling CTC heterogeneity. Next, we will explore methods for generating in vivo CTC-derived xenograft models. Comparing CDX models against CTC culture platforms, we will highlight the advantages and disadvantages of each method and where these models fit within the spectrum of metastasis models. Finally, we will preview how CTC expansion may play a crucial role in the era of personalized medicine.