Cancer stem cell theory and emerging clinical application

New understanding of the basic nature of malignancy is emerging due to novel studies drawing from stem cell biology. Cancer stem cell (CSC) theory proposes that a small subset of cells within a heterogeneous tumour have the capacity to form tumours, and that these cells demonstrate the abilities of stem cells, namely self-renewal and production of a varied repertoire of daughter cells. Evidence points to dysregulated tissue stem cells as the origin of CSCs. This stem cell nature may confer an inherent resistance to conventional cancer treatment, and be responsible for disease recurrence even after a dramatic clinical response. CSCs have been predominantly demonstrated in mouse xenotransplantation studies, where isolated putative CSC cell populations are able to form and recapitulate parent tumours in the host. Several genes related to stem cells and early embryonic development have been found to be active in CSCs and are thought to give CSCs their tumourigenic abilities. These genes also represent potential therapeutic targets, along with the microenvironment that supports the stem cell. Therapies against these targets are in development and include monoclonal antibodies, RNA interference and small molecules. A small number of CSC-specific therapeutics are in early clinical trials. If CSC theory is clinically validated, it stands to dramatically change the way we think of and treat cancer