Role of autophagy in cancer progression and therapy


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Eileen White

Center for Advanced Biotechnology and Medicine, Piscataway, USA

Abstract

Role of autophagy in cancer progression and therapy

Autophagy plays a critical protective role maintaining energy homeostasis and protein and organelle quality control. These functions are particularly important in times of metabolic stress and in cells with high energy demand such as cancer cells. In emerging tumour cells, these protective functions of autophagy prevent cellular damage accumulation and cell death, both of which can foster tumour progression. Autophagy localizes to regions of tumours that are metabolically stressed and defects in autophagy impair the survival of tumour cells in these areas. This impaired survival of autophagy-defective tumour cells is associated with necrotic cell death and inflammation, the cytokine response from which is linked to accelerated tumour growth. In emerging cancer cells, another manifestation of autophagy defect and failure of energy homeostasis and protein and organelle quality control is the activation of the DNA damage response and genome instability. By preventing cellular damage, autophagy may act as a tumour suppression mechanism by limiting the accumulation of mutations that drive tumour progression. The overarching theme is that autophagy protects cells from damage accumulation under conditions of metabolic stress and that this is a critical and novel tumour suppression mechanism. The challenge now is to define the precise aspects of autophagy, including energy homeostasis, or protein and organelle turnover, that are required for the proper management of metabolic stress that suppress tumourigenesis. Furthermore, we need to be able to identify human tumours with deficient autophagy, and to develop rational cancer therapies that take advantage of the altered metabolic state and stress responses inherent to this autophagy defect.