Targeting autophagy in urological system cancers: From underlying mechanisms to therapeutic implications

The urological system, including kidneys, ureters, bladder, urethra and prostate is known to be vital for blood filtration, waste elimination and electrolyte balance. Notably, urological system cancers represent a significant portion of global cancer diagnoses and mortalities. The current therapeutic strategies for early-stage cancer primarily involve resection surgery, which significantly affects the quality of life of patients, whereas advanced-stage cancer often relies on less effective chemo- or radiotherapy. Recently, accumulating evidence has revealed that autophagy, a crucial process in which excess organelles or inclusions within cells are removed to maintain cell homeostasis, has numerous links to urological system cancers. In this review, we focus on summarizing the underlying two-sided mechanisms of autophagy in urological system cancers. We also review the current clinical drugs targeting autophagy, which demonstrate significant potential in improving treatment outcomes for urological system cancers. In addition, we provide an overview of the research status of novel small molecule compounds targeting autophagy that are in the preclinical stages of investigation. Furthermore, drug combinations based on autophagy modulation strategies in urological system cancers are systematically summarized and discussed. These findings provide comprehensive new insight for the future discovery of more autophagy-related drug candidates.