Culture of Circulating Tumor Cells - Holy Grail and Big Challenge

Circulating tumor cells (CTCs), the most important representation of “liquid biopsy”, provides a minimally invasive approach to tumor tissue, and has been a hot topic in cancer research for years. CTCs bear great potential to provide a surrogate for traditional biopsy, and the culture of CTCs is essential to investigate the biological features of CTCs and their roles in cancer metastasis as well as to provide the opportunity for in vitro therapeutic sensitivity tests to guild treatment selection. However, it is challenging to cultivate CTCs due to many factors. 1. They exist in very low numbers in peripheral blood. 2. A large proportion of CTCs may not be viable, and we have not developed reliable analysis tools to distinguish viable from non-viable CTCs. 3. The biological features of CTCs, in particular the favorable environment for their growth, are unclear. Many cell culture methodologies have been tested for CTC propagation and several successful examples have demonstrated the possibility to capture viable CTCs for cultivation, thus inaugurating a new era of CTC research. Long-term culture of CTCs bears great promise as a preclinical model for human cancer, whereas short-term culture is more efficient and gives reasonable molecular information for disease progression status and potential therapeutic responses and targets. In this review, we give a brief summary of CTC isolation and culture strategies, and present published data on CTC culture, either for short-term or long-term, in several major cancer entities. The major challenges in propagation of CTCs have been identified and potential research directions to overcome these difficulties have been proposed.