Targeting Autophagy in Cancer: Therapeutic Implications

Abstract

Autophagy is an evolutionary conserved self-degradation process that occurs ubiquitously in eukaryotes. It plays an important role in maintenance of cellular homeostasis by balancing the energy resources or through removal of misfolded proteins and damaged organelles. During autophagy, the recycling of the long-lived proteins or organelles is executed through their engulfment into double-membrane autophagosome followed by their lysosomal degradation via formation of autophagolysosome. Interestingly, autophagy is under tight regulation by a group of genes called autophagy-related genes (ATG) in association with various signalling pathways. Literature review suggests that autophagy is implicated in numerous developmental and other physiological processes such as cell differentiation, cell survival, cell death, nutrient starvation response and its dysregulation, often, leads to many pathological conditions including cancer. Generally, under normal physiological conditions, basal autophagy occurs in all cells but it is induced only in response to specific intra- or extra-cellular stimuli. In cancer, depending on the context, autophagy can be paradoxical in nature (i.e. tumour-suppressive or tumour-promoting) and has also been documented to have the remarkable role in development of chemoresistance, thus, justifying the effectiveness of cancer therapeutic intervention through stimulation or inhibition of autophagy. Henceforth, in this chapter, we have summarised the autophagy in a nutshell, with focus on its mechanism, monitoring methods, regulation and context-dependent role in cancer and explored how the manipulation of autophagy could be beneficial towards improved cancer cure, as evident from the numerous in vitro and in vivo studies as well as clinical trials.