Targeting cancer cells through autophagy for anticancer therapy.

Autophagy is a cellular degradation process in which portions of the cell's cytoplasm and organelles are sequestered in a double-membrane bound vesicle called an autophagosome. Fusion of autophagosomes with lysosomes results in the formation of autolysosomes, where the proteins and organelles are degraded. This degradation pathway is induced under nutrient deprivation, metabolic stress or microenvironmental conditions to ensure energy balance, clearance of damaged proteins and adaptation to stress. Disruption of autophagy is involved in diverse human diseases including cancer. In particular, the regulation of autophagy in cancer cells is complex since it can enhance tumor cell survival in response to certain stresses, yet it can also act to suppress the initiation of tumor growth. Understanding the signaling pathways involved in the regulation of autophagy as well as the autophagy process itself represents new directions in the development of anticancer therapies. In this review, we discuss recent advances in our understanding the complexity of the autophagy process and the development of targeted therapies that modulate autophagy in cancer cells in the clinic. Copyright 2009. Published by Elsevier Ltd.