Radiosensitization of Cancer Stem Cells: Targeting Tgfî², Notch or Telomerase to Improve Tumor Response O Radiotherapy

Radiation resistant cancer stem cells are the main reason for treatment failure and tumor recurrence after cancer radiotherapy. Increasing biological evidences demonstrate that these cells possess the capacity to repair radiation induced DNA damage, protect themselves from radiation derived reactive oxygen species, survive and proliferate after several fractions of radiotherapy and finally, repopulate the heterogeneity of the tumor. Thus, targeting and eliminating these cells should be necessary to achieve cancer cure in radiotherapy. Three major approaches that specifically target radioresistant cancer stem cells have been recently investigated. First, inhibition of TGF, a major mediator of the tissue response to radiation, has been shown to induce radiosensitization of cancer stem cells by targeting the DNA damage response mechanism. Second, by preventing Notch activation during fractionated radiotherapy, cancer stem cells were depleted from their ability to repopulate the tumor after radiation. Finally, telomerase activity inhibitors have shown to specifically decrease the cancer stem cell population after radiotherapy. In the present review, we evaluate these radiosentitizing approaches and their possible effects when combined with fractionated radiotherapy as they promise to be a powerful tool in the battle against this cancer.