Role of autophagy on anti-cancer drug resistance / 国际药学研究杂志

ABSTRACT

Macroautophagy is a catabolic pathway that degrades cellular components through the lysosomal machinery. Autophagy acts as a survival mechanism under energy depletion-or nutrition deficiency-caused stress as an intracellular quality management system by clearing damaged organelles like mitochondria and proteins. During the early and late stages of cancer development, the role of autophagy differs. In the very early stages of carcinogenesis, autophagy has an important function by reducing cancer initiating genetic instability and aberrant protein aggregates as well as promoting anti-cancer immune response. In established malignant tumors autophagy confers resistance against metabolic stress caused by nutrient deprivation and the rapid proliferation of carcinoma cells. This function of autophagy is also important for radiation and chemotherapy resistance in cancer. Autophagy not only promotes the survival of tumor cells, but also, in special condition, leads to autophagic tumor cell death. During dysfunctional apoptosis this form of cell death mainly sensitizes cancer cells for therapy such as ionizing radiation. Therefore, the functions of autophagy during cancer progression and therapy are two-sided and further research is needed to understand them in greater detail. In this review, the regulation and the role of autophagy in cancer and chemotherapy resistance are discussed.