Cancer stem cells as functional biomarkers in metastasis.

Tumors are heterogeneous diseases as emerged since the earliest pathological examinations. In the clinical setting this heterogeneity is evident, for instance, when we observe patients whose lesions have a different, if not opposite, patterns of response following the delivery of systemic anticancer treatments. We are now beginning to understand branched evolution and tumor heterogeneity at the molecular level, and the lesson learned is that different metastatic lesions, or even different regions within the primary tumor, carry a distinct pattern of genetic abnormalities [1]. While some mutations are conserved across different metastatic sites coexisting in the same patients, others are “private” and confined to a given region or metastatic site [1]. For decades this heterogeneity was explained by the “stochastic” or “clonal evolution model”, that relied on Darwinian principles of evolution [2]. Another model has been proposed following the description of a stringent hierarchical organization in human acute myeloid leukemias [3]. By taking advantage of flow cytometry, tumorigenic and non-tumorigenic cells within the same tumor have been isolated, allowing to envision a pyramidal organization [3]. This model, commonly referred to as the “hierarchical model”, states that the entire tumor population descends from a common progenitor, represented by a CSC at the apex of the pyramid [4]. In this manuscript, we briefly describe the CSC model, key functional properties of CSCs, and how the growing body of knowledge on CSCs has been translated into clinical studies with the purpose of investigating CSC-associated biomarkers or therapeutics for CSC targeting.