Cancer stem cells as functional biomarkers.

According to the American Association of Cancer Research (AACR), a Cancer Stem Cell is a cell within a tumor that possesses the capacity to self-renew and to cause the heterogeneous lineages of cancer cells that constitutes the tumor [1]. Cancer Stem Cells (CSCs) are involved in the metastatic process, in the resistance to therapeutic treatments of many types of human cancers and consequently in the onset of recurrences. Numerous translational studies have been conducted to understand CSC characteristics and evaluate association between CSC-related biomarkers and clinical outcomes. The CSC theory can explain also a tumor relapse after that a tumor has been completely surgically removed (R0 macroscopical zero residual resection) or after an apparently complete response to chemotherapy. CSCs, in fact, showed a marked ability to reduce intracellular accumulation of chemotherapic agents by active drug extrusion, increased chemoresistance and survival, as well as elevated membrane transporter activity. In addition, it is possible that these cancer stem cells may nest in the "secured" (niche) sites of our body, where they may remain undisturbed for a long time, even years, until a stimulus arrives to awaken them, causing the disease to resume. CSCs, in fact, are able to use a variety of cellular pathways to survive to anticancer treatments. More recently CSCs have been described in several solid tumors, expressing specific biomarkers. Another field of research should be focused on the realization of diagnostic instruments to follow up patients after R0 surgical resection or after a complete response for an early detection and management of relapse and metastasis.