Advancements in Circulating Tumor Cell Expansion Ex Vivo: A Matured Technology?

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. Studying the genetic mechanisms involved in the CTC phenotype could enable significant strides in understanding metastasis. Initially, CTC studies were limited in scope to the enumeration of this rare population of cells. However, recent advancements in expanding viable CTCs ex vivo made in the last two decades have enabled researchers to properly interrogate this new frontier of metastatic research, resulting in groundbreaking findings expanding upon the simplistic models of metastasis previously used. In this chapter, we will focus on the technological advancements that have enabled the isolation and propagation of CTCs. First, we will highlight two eras of CTC culture: one focused on growing viable epithelial cells and the other focused on modeling CTC heterogeneity, such as through the capture of CTC clusters. Next, we will explore methods for generating in vivo CTC-derived xenograft (CDX) models. We will further compare and contrast these methods, discussing 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.