Cancer stem cells: Implications for cancer causation and therapy resistance.

Extract: The discovery that many cancers arise from alterations of the body's normal stem cells is changing our views of cancer causation as well as therapy. Stem cells have a unique capacity for self-renewal; with each division they give rise to cells with the same differentiation potential as the parental cell. The replication of stem cells is under tight control. Rapidly dividing tissues such as the hematopoietic (blood) system, the skin, and the gut require perpetually dividing cells, whereas in most tissues, the stem cells are quiescent (inactive) unless stimulated by damage or inflammation. Stem cells are long lived, and therefore have the potential to acquire successive mutations and pass these defects on to daughter cell populations. Normal stem cells possess innate properties that ensure their survival over the lifespan of the individual. This includes the expression of several transport proteins that protect cells against toxins, a low rate of cell division, and active DNA repair. To the extent that cancer stem cells retain these same properties, they will be relatively resistant to radiation and chemotherapy, and may survive to regenerate the tumor. A cancer patient's intestinal lining, white blood cell count, and hair growth recover after cytotoxic therapy because these tissues are renewed from stem cells. In a similar fashion, the patient's tumor may shrink or appear to be eliminated during therapy, but subsequently regress, due to the survival of cancer stem cells.