Autophagy in Cisplatin Nephrotoxicity during Cancer Therapy

SIMPLE SUMMARY: Cisplatin is a broadly used chemotherapy drug, but its use and efficacy are limited by its nephrotoxicity. Autophagy protects against kidney injury during cisplatin exposure but may reduce the efficacy of chemotherapy by protecting cancer cells. In this review, we describe the role and regulation of autophagy in cisplatin-induced nephrotoxicity and discuss the therapeutic advances and challenges of targeting autophagy in chemotherapy. ABSTRACT: Cisplatin is a widely used chemotherapeutic agent but its clinical use is often limited by nephrotoxicity. Autophagy is a lysosomal degradation pathway that removes protein aggregates and damaged or dysfunctional cellular organelles for maintaining cell homeostasis. Upon cisplatin exposure, autophagy is rapidly activated in renal tubule cells to protect against acute cisplatin nephrotoxicity. Mechanistically, the protective effect is mainly related to the clearance of damaged mitochondria via mitophagy. The role and regulation of autophagy in chronic kidney problems after cisplatin treatment are currently unclear, despite the significance of research in this area. In cancers, autophagy may prevent tumorigenesis, but autophagy may reduce the efficacy of chemotherapy by protecting cancer cells. Future research should focus on developing drugs that enhance the anti-tumor effects of cisplatin while protecting kidneys during cisplatin chemotherapy.