Figure 1. CTCs as snapshot of the evolving tumor landscape.

Clonal evolution depicted as emergence of clones after acquisition of driver mutations. New (sub) clones derive from ancestral clones following linear and branched evolution. Outgrowth and repression (therapeutic or outcompeting) of these subclones can lead to emergence and disappearance of driver mutations respectively. Seeding and re-seeding of tumor cells causes development of changing tumor landscapes at multiple sites. Selective therapy pressure can lead to outgrowth of resistant clones at time of disease progression. CTCs sampling can function as a snapshot of the overall tumor bulk (primary tumor and metastases). When profiling CTCs at multiple time points emerging and decreasing subclones can be unveiled. Techniques to profile CTCs include phenotypical and molecular analyses.