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Abstract
Simple SummaryCisplatin 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.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.
Highlights
Cisplatin is a potent chemotherapy drug used for the treatment of various types of tumors [1], but it has remarkable side effects or toxicity in normal tissues [2]
PGC1α may be a key regulator of mitochondrial biogenesis and mitophagy, and PGC1α is a promising target for reducing cisplatin nephrotoxicity in cancer therapy
Mitophagy may be induced as an adaptive response rather than a toxic response in the early phase of kidney injury; it might be impaired in the late stage, and this impairment could be prevented by PGC1α, which accelerates mitochondrial turnover by inducing TFEB to protect against cisplatin acute kidney injury (AKI) [91]
Summary
Cisplatin is a potent chemotherapy drug used for the treatment of various types of tumors [1], but it has remarkable side effects or toxicity in normal tissues [2]. Autophagy is generally considered pivotal in promoting cell survival and protecting against acute cisplatin nephrotoxicity [8,9,10,11]. Autophagy participates in the regulation of maladaptive kidney repair and renal fibrosis after acute kidney injury and during the progression of chronic kidney disease [12,13,14,15,16,17]. Little is known about the role and regulation of autophagy in the development of chronic kidney problems after cisplatin exposure. Autophagy upregulation can protect the kidneys against acute cisplatin injury, but its effect on cancers is context-dependent. This review analyzes the current research about autophagy in cisplatin-induced acute and chronic kidney diseases from its occurrence to function and regulation. We further discuss the therapeutic potential and the challenges of targeting autophagy for kidney protection in cisplatin-mediated chemotherapy
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