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

cAMP induces autophagy via a novel pathway involving ERK, cyclin E and Beclin 1

“…This would be in line with several studies suggesting that autophagy plays a role in radiosensitization rather than protection from radiation therapy. 57,58 It is believed that the role of autophagy in sustaining tissue homeostasis is particularly important in tissues where the cells do not divide after differentiation, such as in neurons and myocytes. 5 For instance, mice with neural-tissue-specific knockdown of the autophagy-related Atg genes will display severe neurodegeneration and neurological dysfunction.…”

Autophagy, senescence and tumor dormancy in cancer therapy

“…5,6 In some studies, autophagy and apoptosis have been found to exert similar levels of toxicity 7,8 while in others a blockade to protective autophagy has resulted in cytotoxicity due to apoptosis. 3,[9][10][11][12] Finally, a recent report presents evidence for apoptosis that is dependent on prior autophagy. The transient arrest and renewed tumor growth that has been interpreted as tumor dormancy by Lu et al 2 is also a common observation in other xenograft models treated with chemotherapy or radiation; 19,20 our own studies in cell culture [21][22][23] also support the concept of drug and radiation induced senescence in tumor cells that is succeeded by proliferative recovery.…”

“…3 However, it remains unclear precisely what factors determine these opposite and clearly opposing functions of autophagy. Although one possible explanation is that the functional consequences of autophagy will depend on the nature and extent of the cellular stress, this interpretation may prove to be too simplistic; there are likely to be as yet undefined biochemical and/or molecular factors that dictate the impact of autophagy on cell survival.…”

“…Interestingly, in the case of radiation, the bulk of the current literature supports the concept that autophagy mediates radiation-induced cell death and confers sensitivity to radiation. 3 Since one of the primary modes of cell death in tumor cells exposed to chemotherapeutic drugs is apoptosis, the relationship between the two cell death modalities of apoptosis and autophagy has been examined quite extensively. 4 Studies have demonstrated reciprocal regulation of autophagy and apoptosis, where a blockade to either apoptosis or autophagy results in expression of the other modality.…”

Autophagy: A potential target for thyroid cancer therapy (Review)

“…The role of autophagy in cancer treatment is complicated and mainly depends on the different context and treatment strategies. Breast tumor cell radiosensitization by vitamin D or vitamin D analogs is mediated through autophagy (31). However, in radioresistant MDA-MB-231 breast cancer cells, autophagy serves as a protective and pro-survival mechanism through promotion of radioresistance mediated by the autophagy inhibitors 3-methyladenine (3-MA) or chloroquine (32).…”