Autophagy in Cancer: Regulation by Small Molecules

During times of stress, autophagy is a cellular process that enables cells to reclaim damaged components by a controlled recycling pathway. This mechanism for cellular catabolism is dysregulated in cancer, with evidence indicating that cancer cells rely on autophagy in the hypoxic and nutrient-poor microenvironment of solid tumors. Mounting evidence suggests that autophagy has a role in the resistance of tumors to standard-of-care (SOC) therapies. Therefore, there is significant interest in the discovery of small molecules that can safely modulate autophagy. In this review, we describe recent advances in the identification of new pharmacological compounds that modulate autophagy, with a focus on their mode of action, value as probe compounds, and validation as potential therapeutics. Autophagy maintains cellular homeostasis during periods of stress. Dysregulation of autophagy has a crucial role in cancer and tumor growth. There are several control points in the autophagic pathway that can be targeted to modulate the process. Small molecules that modulate autophagy by way of inhibition or activation of the autophagic pathway have potential in oncology.