Autophagy in Cancer Therapy—Molecular Mechanisms and Current Clinical Advances

SIMPLE SUMMARY: Autophagy is the capability of cells to dismantle and recycle parts of themselves. This process is closely intertwined with other crucial cell functions, such as growth and control of metabolism. Autophagy is oftentimes dysregulated in cancer and offers established and advanced tumors protection against a lack of nutrients and an advantage regarding proliferation. This review will present an overview of the basics of human autophagy, its dysregulation in cancer, and approaches to target autophagy in cancer treatment in recent and current clinical trials as well as new findings of preclinical research. ABSTRACT: Autophagy is a crucial general survival tactic of mammalian cells. It describes the capability of cells to disassemble and partially recycle cellular components (e.g., mitochondria) in case they are damaged and pose a risk to cell survival or simply if their resources are urgently needed elsewhere at the time. Autophagy-associated pathomechanisms have been increasingly recognized as important disease mechanisms in non-malignant (neurodegeneration, diffuse parenchymal lung disease) and malignant conditions alike. However, the overall consequences of autophagy for the organism depend particularly on the greater context in which autophagy occurs, such as the cell type or whether the cell is proliferating. In cancer, autophagy sustains cancer cell survival under challenging, i.e., resource-depleted, conditions. However, this leads to situations in which cancer cells are completely dependent on autophagy. Accordingly, autophagy represents a promising yet complex target in cancer treatment with therapeutically induced increase and decrease of autophagic flux as important therapeutic principles.