gastric cancer is the second most frequent cause of cancer - related death in the world and almost two - thirds of the cases occur in asian countries , especially china and japan .
although current major therapies , including surgery and chemotherapy , have been widely used , the prognosis of gastric cancer is generally rather poor , with 5-year relative survival below 30% in most countries .
however , the main cause of treatment failure in gastric cancer is the development of multidrug resistance to cytotoxic chemotherapies , which is at least in part related to the anti - apoptosis effect .
it is well known that the resistance of cell death is one of the hallmarks of cancer cells .
although the relationship between autophagy and cancer is still unclear , especially in the regulation of cancer development and progression , there has been much important progress in our understanding that autophagy may have important roles in the treatment of gastric cancer cells .
autophagy is an evolutionarily conserved catabolic process by which damaged or long - lived cellular proteins and organelles are degraded . in the cancer cells it is still unclear
if autophagy represents a survival mechanism or is involved in type ii programmed cell death ( pcd ) , which is termed autophagic cell death .
autophagy is up - regulated when cells need to generate intracellular nutrients and energy , for example , during starvation , growth factor withdrawal , or high bioenergetic demands .
moreover , basal autophagy can serve as an important homeostatic cellular recycling mechanism responsible for degrading unnecessary or dysfunctional cellular organelles and proteins in all living cells ; thus , autophagy can be viewed as a potent cytoprotective survival pathway in normal and cancer cells .
recently , accumulating evidence has indicated that autophagy is particularly activated during metabolic stress such as nutrient depletion and hypoxia , and has a special homeostatic role mediating removal of old or dysfunctional proteins and organelles , and is particularly important for cell survival during conditions of metabolic stress .
moreover , autophagy is the only mechanism for degrading large structures such as protein aggregates and damaged organelles .
although autophagy has been induced in many different cancer cell lines , including gastric cancer cells using different agents such as chemotherapeutics , the role of autophagy in tumor cell death or survival is still unclear .
autophagy has several adaptive roles in diverse human pathologies , including cancer and other diseases , and can act as a cytoprotective survival pathway . thus , under many conditions , autophagy is induced in response to many different forms of stress , including nutrient and growth factor deprivation and chemotherapeutics , and is utilized as a protective mechanism against cell death in the hostile environment .
in fact , more and more results have suggested that autophagy can provide a survival advantage to tumors treated with chemotherapeutic agents . in human hepatocellular carcinoma and colorectal carcinoma cells ,
moreover , inhibition of autophagy by 3-methyladenine ( 3-ma ) can potentiate cisplatin - induced apoptosis in esophageal squamous cell carcinoma cells .
in addition , many studies have revealed that inhibition of autophagy can augment cancer cell death through apoptosis , which indicates that autophagy may act as a protector in tumor cell survival .
furthermore , other studies have proved that induction of autophagy can enhance tumor resistance in different tumor cell lines .
hypoxia - induced autophagy can decrease hepatoma cell sensitization to chemotherapeutic agents that affect their apoptotic potential . in gastric cancer cells
thus , results of many studies suggest that induction of autophagy can protect tumor cells against cancer treatment .
previous studies have shown that inhibition of autophagy can potentiate the cell death induced by anticancer drugs in gastric cancer cells [ 1921 ] .
therefore , we speculate that inhibition of autophagy may be a strategy for overcoming gastric cancer resistance to therapy .
in recent years , the role of autophagy in cancer cells has been investigated extensively .
although the impact of autophagy on tumor cells is still unclear and more studies are needed to prove the effects of autophagy in gastric cancer , recent research results suggest that autophagy may be a new target for combatting resistance of gastric cancer to therapy .
 gastric cancer is the second most frequent cause of cancer - related death in the world and also causes much morbidity . 
 the acquired resistance of cancer cells to drug reagents is becoming a major obstacle for successful cancer therapy . 
 recently , many studies have revealed that macroautophagy ( here referred to as autophagy ) may be a prosurvival factor and protect the cancer cell from the development of drug - induced death . 
 thus , we propose that autophagy may play an important role in the resistance of gastric cancer to therapy . 
 although the exact role of autophagy in tumor cells is still unclear and further studies are needed to prove the role of autophagy in gastric cancer , recent research findings suggest a new direction in investigating the mechanism underlying resistance of gastric cancer to therapy . 