Promotion of autophagy as a mechanism for radiation sensitization of breast tumor cells.

Radiation has long been a useful component of the treatment regimen for solid tumors. However, some malignancies are relatively resistant to radiation treatment while even tumors that may initially respond (to both radiation and chemotherapy) may eventually recover proliferative capacity. A variety of approaches have been utilized in the efforts to enhance radiation sensitivity. Recent studies have identified autophagy as a cell death pathway that may mediate the radiosensitizing effects of selected treatments. Studies in our laboratory support the premise that radiosensitization of breast tumor cells by vitamin D or vitamin D analogs is mediated through autophagy. In addition, promotion of autophagic cell death by a vitamin D analog in irradiated breast tumor cells delays and attenuates the proliferative recovery that may be a preclinical indicator of disease recurrence.