Effect of Autophagy on Chemotherapy-Induced Apoptosis and Growth Inhibition

Cancer cells are resistant to chemotherapy, which results in poor prognosis for cancer patients. Autophagy, a self-eating process, has been widely reported as a prosurvival mechanism underlying cancer cell chemo-resistance. Upon chemotherapeutics treatment, autophagy is employed by cancer cells to maintain cellular homeostasis and mitigate genome damage by degrading damaged proteins and organelles such as mitochondria, thus preventing cell apoptosis. In the tumor microenvironment characteristic of oxygen and nutrient deprivation, autophagy is activated in cancer cells to cope with metabolic stress, and these cells were more refractory to chemotherapy. Cancer stem cells (CSCs) are a subset of cancer cells that can evade cell death induced by existing chemotherapeutic agents, and one of the underlying mechanisms might be autophagy. Emerging evidence shows that CSCs have higher levels of autophagy under normal conditions and ischemic and hypoxic conditions. Autophagy inhibition could sensitize non-CSCs and CSCs to chemotherapy-induced apoptosis and growth inhibition; thus, it is under consideration for being developed as a synergistic therapy with existing chemotherapies for better therapeutic effects.