TY - JOUR
T1 - Cisplatin nephrotoxicity
T2 - new insights and therapeutic implications
AU - Tang, Chengyuan
AU - Livingston, Man J.
AU - Safirstein, Robert
AU - Dong, Zheng
N1 - Funding Information:
The authors’ work was supported in part by grants from the National Natural Science Foundation of China (81870474), the National Institutes of Health (DK058831, DK087843) and the US Department of Veterans Affairs (BX000319). Z.D. is a recipient of the Senior Research Career Scientist award from the US Department of Veterans Affairs.
Publisher Copyright:
© 2022, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.
PY - 2023/1
Y1 - 2023/1
N2 - Cisplatin is an effective chemotherapeutic agent for various solid tumours, but its use is limited by adverse effects in normal tissues. In particular, cisplatin is nephrotoxic and can cause acute kidney injury and chronic kidney disease. Preclinical studies have provided insights into the cellular and molecular mechanisms of cisplatin nephrotoxicity, which involve intracellular stresses including DNA damage, mitochondrial pathology, oxidative stress and endoplasmic reticulum stress. Stress responses, including autophagy, cell-cycle arrest, senescence, apoptosis, programmed necrosis and inflammation have key roles in the pathogenesis of cisplatin nephrotoxicity. In addition, emerging evidence suggests a contribution of epigenetic changes to cisplatin-induced acute kidney injury and chronic kidney disease. Further research is needed to determine how these pathways are integrated and to identify the cell type-specific roles of critical molecules involved in regulated necrosis, inflammation and epigenetic modifications in cisplatin nephrotoxicity. A number of potential therapeutic targets for cisplatin nephrotoxicity have been identified. However, the effects of renoprotective strategies on the efficacy of cisplatin chemotherapy needs to be thoroughly evaluated. Further research using tumour-bearing animals, multi-omics and genome-wide association studies will enable a comprehensive understanding of the complex cellular and molecular mechanisms of cisplatin nephrotoxicity and potentially lead to the identification of specific targets to protect the kidney without compromising the chemotherapeutic efficacy of cisplatin.
AB - Cisplatin is an effective chemotherapeutic agent for various solid tumours, but its use is limited by adverse effects in normal tissues. In particular, cisplatin is nephrotoxic and can cause acute kidney injury and chronic kidney disease. Preclinical studies have provided insights into the cellular and molecular mechanisms of cisplatin nephrotoxicity, which involve intracellular stresses including DNA damage, mitochondrial pathology, oxidative stress and endoplasmic reticulum stress. Stress responses, including autophagy, cell-cycle arrest, senescence, apoptosis, programmed necrosis and inflammation have key roles in the pathogenesis of cisplatin nephrotoxicity. In addition, emerging evidence suggests a contribution of epigenetic changes to cisplatin-induced acute kidney injury and chronic kidney disease. Further research is needed to determine how these pathways are integrated and to identify the cell type-specific roles of critical molecules involved in regulated necrosis, inflammation and epigenetic modifications in cisplatin nephrotoxicity. A number of potential therapeutic targets for cisplatin nephrotoxicity have been identified. However, the effects of renoprotective strategies on the efficacy of cisplatin chemotherapy needs to be thoroughly evaluated. Further research using tumour-bearing animals, multi-omics and genome-wide association studies will enable a comprehensive understanding of the complex cellular and molecular mechanisms of cisplatin nephrotoxicity and potentially lead to the identification of specific targets to protect the kidney without compromising the chemotherapeutic efficacy of cisplatin.
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U2 - 10.1038/s41581-022-00631-7
DO - 10.1038/s41581-022-00631-7
M3 - Review article
C2 - 36229672
AN - SCOPUS:85139934530
SN - 1759-5061
VL - 19
SP - 53
EP - 72
JO - Nature Reviews Nephrology
JF - Nature Reviews Nephrology
IS - 1
ER -