An overview of autophagy inhibition as a potential clinical strategy in cancer therapy.

Autophagy is a cellular process responsible for the recycling of misfolded proteins and damaged organelles, contributing to cellular homeostasis and energy production. Tumor cells often exploit this mechanism, particularly through the form of autophagy that is cytoprotective, to survive endogenous and exogenous stress and resist chemotherapeutic agents as well as radiation therapy. Although several autophagy inhibitors have been developed to block the protective form of autophagy, their clinical application is often limited due to a lack of selectivity and significant side effects. In addition to the cytoprotective form, cytotoxic, cytostatic, and nonprotective functions of autophagy have been identified. In this review, we summarize a series of publications, largely from our own laboratory, exploring how various antineoplastic agents trigger different forms of autophagy and assess whether autophagy inhibition or modulation could serve as an effective adjuvant approach to enhance therapeutic responses. Furthermore, we discuss recent advancements in the autophagy field and the potential for improving cancer therapeutic strategies. SIGNIFICANCE STATEMENT: This work provides an overview of our previous work investigating the different forms of autophagy induced by various antineoplastic modalities across different tumor models. The purpose of this effort is to draw tentative conclusions regarding the potential of targeting autophagy as a strategy to enhance the efficacy of these therapeutic agents. Additionally, we offer insights into recent advances in the autophagy field.