Autophagy, or 'self-eating', is an adaptive process that enables cells to cope with metabolic, toxic, and even infectious stressors. Although the adaptive capability of autophagy is generally considered beneficial, autophagy can also enhance nutrient utilization and improve growth characteristics of
cancer cells. Moreover, autophagy can promote greater cellular robustness in the context of therapeutic intervention. In advanced
prostate cancer, preclinical data provide evidence that autophagy facilitates both
disease progression and therapeutic resistance. Notably,
androgen deprivation
therapy,
taxane-based
chemotherapy, targeted
kinase inhibition, and nutrient restriction all induce significant cellular distress and, subsequently, autophagy. Understanding the context-dependent role of autophagy in
cancer development and treatment resistance has the potential to improve current treatment of advanced
prostate cancer. Indeed, preclinical studies have shown that the pharmacological inhibition of autophagy (with agents including
chloroquine,
hydroxychloroquine,
metformin, and
desmethylclomipramine) can enhance the cell-killing effect of
cancer therapeutics, and a number of these agents are currently under investigation in clinical trials. However, many of these autophagy modulators are relatively nonspecific, and cytotoxicity in noncancerous tissues is still a concern. Moving forward, refinement of autophagy modulation is needed.