CTCs are a subpopulation of aggressive tumor cells that can migrate from the primary tumor through the blood vessels to reach distal organs and form metastases.

CTCs are able to strongly modify their phenotype to survive in the blood vessels. They become resistant to anoikis, the programmed cell death that occurs when a cell detaches from a solid structure, evade immune surveillance, extravasate into a distal organ, and ultimately to form metastases.  

Not much is known about these cells, particularly because they are very rare and very difficult to isolate from patients’ blood samples. Understanding the mechanisms behind their formation and survival in the bloodstream, would greatly advance our knowledge of metastases biology and could aid in the development of a new generation of drugs capable of blocking metastasis formation, thereby significantly reducing cancer mortality.

Furthermore, CTCs could become a valuable source for liquid biopsies, especially in cancers where surgery is not feasible.

After preliminary in vitro investigations, in which we studied the effects of hypoxia and radiation on the primary tumor in generating a subpopulation of cells with CTCs-like phenotype, our group began exploring new methods to isolate CTCs from in vivo models.

Successfully isolating these cells has allowed us to collect new data on their phenotype and transcriptomic profile. Initial results indicate that CTCs are highly heterogeneous, but they all show significant differences in gene expression compared to the primary tumor (figure 2).