Mechanistic Insights into Autophagosome-Lysosome Fusion in Cancer Therapeutics

Abstract

Autophagy is a highly conserved metabolic process to degrade cytoplasmic materials, damaged organelles and aggregated milieus through formation of autolysosome with the help of lysosomal acid hydrolases. This multistep event has a dual role in the regulation of cancer. The termination step of autophagy involving fusion of autophagosome and lysosome degrades autopahgic cargo to establish the cellular homeostasis. This is the point which defines the cytoprotective nature of autophagy in some cases and on the contrary, it also acts as tumor suppressor step due to accumulation of autophagic vacuoles or excessive autopahgic flux in most of the cancers. In this setting, many different drugs have been developed and discovered to combat the various type of cancers through the modulation of autophagy in the cancer cells either by its activation or suppression mechanism. Interestingly, targeting the genes of stage-specific regulation of autophagy could be a novel approach for the directive suppression and prevention of cancer. Moreover, the endocytosis-autophagy crosstalk gives an edge to develop drugs which specifically acts upon the cancer cells and modulate the autophagy process. In addition, the drugs modulating the fusion step of autophagy may be the novel molecule for the cancer therapeutics which needs to be investigated further for future cancer treatment.