The role of autophagy in cancer development and response to therapy

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Abstract
Autophagy is a process that describes the degradation and recycling of proteins and intracellular components in response to starvation or stress. At the early stage of tumour development, autophagy functions as a tumour suppressor. Expression of beclin 1 (BECN1), a mammalian orthologue of the yeast autophagy-related gene Atg6, reduces tumorigenic capacity through induction of autophagy. Mice that are Becn1+/− display a remarkable increase in the incidence of lung cancer, hepatocellular carcinoma and lymphoma. At advanced stages of tumour development, autophagy promotes tumour progression. The tumour cells that are located in the central area of the tumour mass undergo autophagy to survive low-oxygen and low-nutrient conditions. Autophagy protects some cancer cells against anticancer treatments by blocking the apoptotic pathway ('protective autophagy'). By contrast, other cancer cells undergo autophagic cell death after cancer therapies. Autophagy is induced mainly through the phosphatidylinositol 3-phosphate kinase (PI3K)–AKT–mTOR (mammalian target of rapamycin) signalling pathway. Manipulation of autophagy has the potential to improve anticancer therapeutics. When tumour cells induce protective autophagy, inhibition of autophagy could sensitize tumour cells to the treatment by activating apoptosis. On the other hand, induction of autophagic cell death can also have a therapeutic value.
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