CTCs are isolated with microfluidics technologies from the peripheral blood of patients with cancer. We believe that CTC analysis is not only an exceptional opportunity to define the characteristics and vulnerabilities of metastatic precursors, but it also represents a non-invasive source to study:
- the involvement of specific cell-cell junction components in the formation of CTC-clusters
- the molecular determinants of organ-specific metastasis
- the evolving mutational profile of metastatic cancers during the course of treatment and disease progression.
For example, molecular analysis of human CTC-clusters has revealed that these metastatic precursors rely upon the expression of specific cell-cell junction components such as plakoglobin (Aceto et al., Cell, 2014). Expression of several other cell-cell junction markers is also evident in human CTC-clusters (see Figure 3).
We believe that targeting cell-cell junctions may represent a potent and previously under appreciated strategy to suppress CTC-clustering and cancer metastasis.
Additionally, human CTCs from patients with metastatic breast cancer have been first isolated, and then propagated ex vivo using specific culture conditions. Genome sequencing of those CTC-derived cell lines revealed patient-specific mutations, and along with ex vivo drug screening, this approach helped to identify the best therapy for individual cancer patients over the course of their metastatic disease (Yu, Bardia, Aceto et al., Science, 2014).