Figure 2. Conceptual schematic of autophagy as a tumor suppressor, tumor supporter, and mediator of chemotherapy resistance.

In the absence of stress signals, normal cells require autophagy to maintain homeostasis. Stress signals such as DNA damage or reactive oxygen species induce autophagy, which recycles damaged proteins and organelles and prevents transformation. Autophagy therefore serves as a tumor suppressor in normal cells. If the accumulation of damage exceeds autophagic capacity (flux), transformation to a cancer cell can occur. Thereafter, autophagy supports tumorigenesis by supplying recycled building blocks and energy to tumor cells while also clearing damage. Cells that sustain high autophagy or acquire a gain-offunc tion mutation are likely to progress to an aggressive tumor. A majority of conventional anti-cancer treatments stimulate autophagy, which imparts drug resistance. Therefore, combination therapies that include an inhibitor are expected to enhance anticancer efficacy.