Figure 3. Application of autophagy modulation to cancer therapy.

a | In apoptosis-defective tumours that are reliant on autophagy to survive metabolic stress, autophagy inhibitors can be used to induce acute necrotic cell death that may be facilitated by proteasome inhibition, enabling tumour eradication. b | In the adjuvant setting, and after elimination of a large proportion of the tumour by radiation and chemotherapy, the remaining cells can reside in a disrupted and stressed environment, susceptible to inhibition of the autophagy survival mechanism. Tumour cells in the process of metastasis can be similarly vulnerable. c | Autophagy stimulators may be therapeutically useful to either promote autophagic cell death or to prevent the damaging effects of autophagy deficiency and mismanagement of metabolic stress leading to DNA damage and tumour progression. By limiting protein, organelle and ultimately DNA damage, autophagy stimulators may suppress tumour progression. In human breast, ovarian and prostate cancers, where allelic loss of BECN1 occurs with high frequency, correction of the autophagy deficiency with autophagy stimulators may delay tumour progression by reducing the rate at which tumour-promoting mutations accumulate.