Fig. 3

The reactivation of the p53 safety switch rescues cells from a malignant cancer stem cell fate. Research strategies for cancer stem cells might be developed from pluripotent stem cell technology. Based on the recent discovery of cancer stem cells and on iPSC studies, we look forward to the development of treatment strategies for cancer stem cells with pluripotent stem cell-like properties (pluripotent stem cell-like CSCs). The green sphere represents normal iPSCs, which are located at the top of the developmental hill. The red sphere represents a cancer stem cell with certain safety system defects, such as p53 loss, retinoblastoma protein (Rb) deletion, and RAS abnormalities, among others. Pluripotent stem cell-like CSCs may be located at a certain point along the pathway down the developmental hill and may be transferable or may metastasize to other locations. Cancer stem cells might have p53 loss or multiple gene function abnormalities that affect, for example, Rb and N-ras. We hypothesize a method to restrict cancer stem cells with abnormal p53-Rb-Nras signaling pathway disorders. This objective could be achieved through the reactivation of p53, the activation of Rb, and the correction of the abnormal N-ras gene or other genes via a similar process to that used to inhibit cancer stem cells and reach final treatment goals. a Tumor stem cells can exhibit abnormal stem cell differentiation (red sphere). They can freely transfer to other points on the developmental hill, including the location that represents pluripotent stem cell-like cells. b If the normal activity of p53 is restored, p53 can limit cancer stem cells by inducing the loss of most stem cell properties. c Other types of cancer stem cells might require the reactivation of two genes, such as Rb and p53, that are restricted or inhibited to cause these cells to lose their metastatic potential. d To control the most powerful cancer stem cells, it might be necessary to reactivate all three pathways. These cells will then be forced to completely differentiate, causing them to lose their invasiveness and their metastatic and/or proliferative potential